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Sodium iron NaFeEDTA as an iron fortification compound in Central America. Absorption studies.

Studies were performed in seven children and 98 adults to compare the proportion of iron absorbed when administered as ferric sulfate (Fe2(SO4)3), NaFeEDTA, hemoglobin (Hb), and ferrous ascorbate. Studies in children (mostly iron deficient) showed that when the compounds were given with a milk-rice-sugar formula totalling 5 mg Fe, iron from hemoglobin was absorbed best, followed by NaFeEDTA and by Fe2(SO4)3 (mean percent absorption +/-SD = 34.5 +/- 1.5, 8.6 +/- 1.9 and 3.3 +/- 1.5, respectively). Studies in normal or iron deficient adults also demonstrated a better absorption of iron from NaFeEDTA than from Fe2(SO4)3 whether these compounds were given in an aqueous solution (5 mg Fe) or with a standard meal consisting of beans, tortillas, bread, and coffee providing also a total of 5 mg Fe. Hb iron under the same conditions was absorbed in the same proportion to the reference iron ascorbate, always being higher than iron absorbed from the other compounds. Fe2(SO4)3 and NaFeEDTA mixed in the same meal were absorbed in the same proportion as when NaFeEDTA alone was added to the meal and 2 to 3 times better than when Fe2(SO4)3 alone was added to the meal. Addition of desferrioxamine depressed iron absorption from Fe2(SO4)3 and NaFeEDTA, the latter being less affected. Addition of ascorbic acid increased absorption from both. When the compounds were added to the meal to provide 50 mg of iron, percent absorption was depressed in relation to the smaller iron dose in the case of Fe2(SO4)3 and Hb but remained unaltered in the case of NaFeEDTA. Addition of 45 mg Fe as Fe2(SO4)3 or NaFeEDTA to 0.4 mg Fe from the Hb in the meal did not change Hb iron absorption. Addition of 45 mg Fe as Hb or NaFeEDTA to 0.4 mg Fe from Fe2(SO4)3 in the meal enhanced iron absorption from the latter in the same proportions. Addition of 45 mg Fe as Fe2(SO4)3 and Hb to 0.4 mg Fe as NaFeEDTA in the meal respectively depressed and enhanced iron absorption from NaFeEDTA. These studies indicate that NaFeEDTA, Fe2(SO4)3 and nonheme food iron from a common pool different from the heme pool but which is changed in its characteristics by the presence of NaFeEDTA, resulting in a better absorption of iron.

Absorption↗

Mixture models for detecting differentially expressed genes in microarrays.

An important and common problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. As this problem concerns the selection of significant genes from a large pool of candidate genes, it needs to be carried out within the framework of multiple hypothesis testing. In this paper, we focus on the use of mixture models to handle the multiplicity issue. With this approach, a measure of the local FDR (false discovery rate) is provided for each gene. An attractive feature of the mixture model approach is that it provides a framework for the estimation of the prior probability that a gene is not differentially expressed, and this probability can subsequently be used in forming a decision rule. The rule can also be formed to take the false negative rate into account. We apply this approach to a well-known publicly available data set on breast cancer, and discuss our findings with reference to other approaches.

Animals↗

Upper and lower limb muscle power relationships in mobility-limited older adults.

BACKGROUND: Lower limb muscle power impairments are modifiable factors underlying mobility limitations in older adults. This study examined relationships between upper and lower limb muscle power and their role in predicting mobility performance among community-dwelling older adults. METHODS: A cross-sectional analysis was conducted. Participants included 37 mobility-limited adults (24 women, 13 men), aged 65 to 93 years. Measures included upper (elbow extension) and lower limb (double leg press) one repetition maximum (1RM), and muscle power at both 40% and 70% one repetition maximum. Physical performance measures included stair climb time, the Short Physical Performance Battery, and 4-meter walk time. Factors commonly mediating the relationship between impairments and physical performance were analyzed as covariates. RESULTS: Participants had a mean age of 76 years, had five chronic medical conditions, and manifested moderate mobility limitations. Although the associations between the upper and lower limbs were strong (p <.001), the magnitude of association was greater for power (r =.88-.89) as compared to strength (r =.69). Multivariate regression analyses revealed consistently strong relationships between limb muscle power and mobility performance measures. Substituting upper for lower limb power within these models did not materially weaken the relationships. CONCLUSION: Muscle power appears to be a more generalized attribute between the upper and lower limbs than is muscle strength, suggesting that mechanisms underlying velocity of movement, as opposed to force production, may be important factors underlying muscle power in elderly persons. Additionally, upper limb muscle power measures may serve as a useful surrogate measure of limb power having implications for clinicians and researchers.

Aged↗

The regulation of sugar uptake and accumulation in bean pod tissue.

The identity, localization and physiological significance of enzymes involved in sugar uptake and accumulation were determined for endocarp tissue of pods of Kentucky Wonder pole beans (Phaseolus vulgaris). An intracellular, alkaline invertase (pH optimum, 8) was assayed in extracted protein, as well as enzymes involved in sucrose synthesis, namely, uridinediphosphate (UDP-glucose pyrophosphorylase and UDP-glucose-fructose transglucosylase). Indirect evidence indicated the presence also of hexokinase, phosphohexoseisomerase and phosphoglucomutase. The data suggested that sucrose synthesis occurred in the cytoplasm, and that both sugar storage and an alkaline invertase occurred in the vacuole. The latter functions to hydrolyze accumulated sucrose. An outer space invertase (pH optimum, 4.0) was detected, but was variable in occurrence. Although its activity at the cell surface enhanced sucrose uptake, sucrose may be taken up unaltered.Over a wide range of concentrations of exogenous glucose the sucrose/reducing sugar ratio of accumulated sugars remained unchanged at about 20. Synthesis of sucrose appears to be requisite to initial accumulation from glucose or fructose, as free hexoses do not increase at the apparent saturating concentration for uptake. Sucrose accumulation from exogenous hexose represents a steady-state value, in which sucrose is transported across the tonoplast into the vacuole at a rate equivalent to its rate of synthesis. Evidence indicates that this component of the accumulation process involves active transport of sucrose against a concentration gradient. The ratio of sucrose/reducing sugars in the accumulated sugars immediately after a period of uptake was inversely related to the level of inner space invertase. Within 16 hours after a period of accumulation, practically all of the sugar occurs as glucose and fructose.The absence of competition among hexoses and sucrose indicated that a common carrier was not involved in their uptake. From a series of studies on the kinetics of uptake of glucose and fructose, including competition studies, the effects of inhibitors, radioactive assay of accumulated sugars and the distribution of label in accumulated sucrose it appeared that rate limitation for glucose or fructose uptake resides in the sequence of reactions leading to sucrose synthesis, rather than in a process mediated by a carrier protein.

Journal Article↗

Inpatient treatment of the psychiatric patient with alcoholism.

Patients with both alcoholism and mental illness, or the one masquerading as the other, are very common and often puzzling and discouraging to clinicians. This article reviews several aspects of these problems: epidemiologic studies show that substantial proportions of mentally ill people suffer from alcoholism, and these disorders interlock in complex ways, each exacerbating the other. Many physicians feel uncomfortable working with alcoholic people, mostly because of poor training, and this impinges on difficulties of giving excellent care to these taxing patients. Complexities and resistances to interviewing obstruct evaluation. Interviewing and history taking techniques and the reason for them are discussed. The decision whether a patient needs medical or psychiatric hospitalization, alcoholism rehabilitation, or outpatient psychiatric or alcoholism treatment is reviewed along with the management and sequencing of treatment for primary and secondary alcoholism with concomitant psychosis, mania, depression, panic disorder, and adult attention deficit disorder. Clinical intervention and referral for the patient on a medical or surgical floor who may have alcoholism is discussed. Two special clinical problems, the differential diagnosis of postdetoxification depression and the risks of using alcohol cross-tolerant drugs, are also reviewed.

Alcoholism↗

Does insulin resistance unite the separate components of the insulin resistance syndrome? Evidence from the Miami Community Health Study.

A number of coronary heart disease risk factors have been identified that often cluster together to increase the risk of macrovascular disease. This cluster is referred to as the insulin resistance syndrome, and the risk factors commonly include dyslipidemia, elevated blood pressure, an android pattern of body fat distribution, and glucose intolerance. Whether hyperinsulinemia or insulin resistance per se provides a common pathway for these metabolic abnormalities is unclear. The authors studied 50 nondiabetic persons who had completed a euglycemic hyperinsulinemic clamp protocol in addition to a 75-g oral glucose tolerance test and other measures of the coronary risk profile. Using principal-component analysis, we reduced nine coronary risk factors to two uncorrelated factors that explained 54.5% of the variance. Factor 1 consisted of positive loadings for uric acid, systolic and diastolic blood pressure, triglyceride concentration, and waist girth and negative loadings for HDL cholesterol and the rate of insulin-mediated glucose disposal (M, in milligrams per kilogram of body weight per minute). M also loaded on factor 2, along with fasting insulin and glucose concentrations, diastolic blood pressure, and waist girth. The observation that M loaded on both factors suggests that a resistance to insulin action may provide the mechanism uniting the features of the insulin resistance syndrome. Hyperinsulinemia with concomitant insulin resistance may be necessary to produce this metabolic derangement, as well as the increased risk of macrovascular complications.

Adult↗

Compositional evaluation of some cowpea varieties and some under-utilized edible legumes in Nigeria.

The nutritive potentials of some cowpea varieties such as Ife Brown, Ife Bimpe, IT84E-124, K59 and TVX716 and some under-utilized edible legumes grown in Nigeria such as pigeon pea (Cajanus cajan), lima bean (Phaseolus lunatus), lablab bean (Dolichos lablab), mucuna bean (Mucuna sp.) and Sphenostilis sternocarpa have been evaluated with respect to their proximate chemical composition, mineral content and some endogenous toxic constituents. The cowpea varieties contained on the average 22.5 g crude protein (CP), 2.60 g crude fibre (CF), 5.89 g either extract (EE) and 3.36 g ash/100 g DM while the under-utilized legumes contained 21.7, 6.10, 2.86, and 3.56 g/100 g DM for CP, CF, EE and ash respectively. Distinct varietal differences were observed for EE values as indicated by the coefficients of variation (CV) of 102% for cowpea and 60.8% for the under-utilized legumes. The CF content of the under-utilized legumes were generally higher than those of the cowpea varieties. Potassium was the most abundant mineral in both the cowpea varieties and the under-utilized legumes with mean values of 1.45 and 1.66% respectively, while P was the least abundant with 13.1 and 8.50 ppm, respectively. There were marked intra-varietal differences in the P content as shown by the high CV of 84.0 and 73.9% for the cowpea varieties and the other legumes. The cowpea varieties generally had higher levels of thioglucosides, trypsin inhibitor activity (TIA) and lower haemagglutinating activity (mean values of thioglucosides: 3.86%, of TIA: 13.9 mg/g protein and of haemagglutinating activity: 13.0 HU/mg N respectively), than the under-utilized legumes with mean respective values of 1.22%, 9.84 mg/g protein and 22.7 HU/mg N. The nutritional implications of these anti-nutritional components were discussed and some reasons adduced for the under-utilization of some of these legumes inspite of their apparent similarity in nutritional quality to the more commonly consumed grain legumes.

Calcium↗

Influence of the size of indigenous rhizobial populations on establishment and symbiotic performance of introduced rhizobia on field-grown legumes.

Indigenous rhizobia in soil present a competition barrier to the establishment of inoculant strains, possibly leading to inoculation failure. In this study, we used the natural diversity of rhizobial species and numbers in our fields to define, in quantitative terms, the relationship between indigenous rhizobial populations and inoculation response. Eight standardized inoculation trials were conducted at five well-characterized field sites on the island of Maui, Hawaii. Soil rhizobial populations ranged from 0 to over 3.5 x 10 g of soil for the different legumes used. At each site, no less than four but as many as seven legume species were planted from among the following: soybean (Glycine max), lima bean (Phaseolus lunatus), cowpea (Vigna unguiculata), bush bean (Phaseolus vulgaris), peanut (Arachis hypogaea), Leucaena leucocephala, tinga pea (Lathyrus tingeatus), alfalfa (Medicago sativa), and clover (Trifolium repens). Each legume was (i) inoculated with an equal mixture of three effective strains of homologous rhizobia, (ii) fertilized at high rates with urea, or (iii) left uninoculated. For soybeans, a nonnodulating isoline was used in all trials as the rhizobia-negative control. Inoculation increased economic yield for 22 of the 29 (76%) legume species-site combinations. While the yield increase was greater than 100 kg ha in all cases, in only 11 (38%) of the species-site combinations was the increase statistically significant (P </= 0.05). On average, inoculation increased yield by 62%. Soybean (G. max) responded to inoculation most frequently, while cowpea (V. unguiculata) failed to respond in all trials. Inoculation responses in the other legumes were site dependent. The response to inoculation and the competitive success of inoculant rhizobia were inversely related to numbers of indigenous rhizobia. As few as 50 rhizobia g of soil eliminated inoculation response. When fewer than 10 indigenous rhizobia g of soil were present, economic yield was significantly increased 85% of the time. Yield was significantly increased in only 6% of the observations when numbers of indigenous rhizobia were greater than 10 cells g of soil. A significant response to N application, significant increases in nodule parameters, and greater than 50% nodule occupancy by inoculant rhizobia did not necessarily coincide with significant inoculation responses. No less than a doubling of nodule mass and 66% nodule occupancy by inoculant rhizobia were required to significantly increase the yield of inoculated crops over that of uninoculated crops. However, lack of an inoculation response was common even when inoculum strains occupied the majority of nodules. In these trials, the symbiotic yield of crops was, on average, only 88% of the maximum yield potential, as defined by the fertilizer N treatment. The difference between the yield of N-fertilized crops and that of N(2)-fixing crops indicates a potential for improving inoculation technology, the N(2) fixation capacity of rhizobial strains, and the efficiency of symbiosis. In this study, we show that the probability of enhancing yield with existing inoculation technology decreases dramatically with increasing numbers of indigenous rhizobia.

Journal Article↗

A new approach to quantitate carbohydrate-deficient transferrin isoforms in alcohol abusers: partial iron saturation in isoelectric focusing/immunoblotting and laser densitometry.

Carbohydrate-deficient transferrin (Tf) represents a significant advance over previous markers of alcohol abuse. Isoelectric focusing (IEF) analysis of affinity-purified Tf, under conditions of total iron saturation, identifies a major isoform at pI 5.4 in both normal consumers and alcohol abusers; three additional Tf isoforms (pI 5.6, 5.7, and 5.8) are associated with alcohol abuse. Under conditions of partial iron saturation, IEF analysis of affinity-purified Tf reveals up to seven isoforms (pI range 5.3-6.0) common to normal consumers and alcohol abusers; three additional transferrin isoforms (pI range 6.1-6.3) are present in 68% (15/22) of the alcohol abuser specimens, but in only 8% (1/12) of the specimens from normal consumers and in none of the three specimens from abstainers. These three diagnostic bands comigrate with a set of defined Tf isoforms: human iron-free Tf containing two sialic acid residues, human sialic acid-free Tf with one iron molecule, and human sialic acid-free, iron-free Tf. Serum specimens from normal consumers and alcohol abusers, analyzed for Tf isoforms by an IEF-immunoblot method under conditions of partial iron saturation, expressed Tf isoforms similar to those found using affinity-purified Tf in standard IEF. Visual examination of the immunoblots reveals the diagnostic bands in 67% (32/48) of patients with histories of sustained alcohol abuse compared with only 17% (8/48) of the normal consumers. Scanning densitometry and volume integration analysis of the immunoblots representative of normal consumer and alcohol abuser populations results in mean (+/- SE) values of 4.1 +/- 0.8 and 19.3 +/- 3.6 units, respectively (p < 0.0002).

Adult↗

Effects of high osmotic strength on chromosome aberrations, sister-chromatid exchanges and DNA strand breaks, and the relation to toxicity.

Substantial increases in chromosome aberrations were induced in Chinese hamster ovary cells by medium made hyperosmotic with NaCl, KCl, sucrose, sorbitol or dimethyl methylphosphonate. The increases were associated with cytotoxicity but occurred in the range (e.g., 70% survival) commonly included in in vitro tests for 'genotoxicity'. The relation between increased osmotic pressure and chromosome aberrations is compound-dependent, e.g., some compounds may have a direct effect in addition to an effect mediated by osmotic pressure/ionic strength. Also, glycerol at high osmolality was not toxic and did not induce aberrations, probably because rapid equilibration across the cell membrane precluded severe osmotic stress to the cells. Weak increases in DNA single-strand breaks (NaCl and KCl) and double-strand breaks (NaCl) were also detectable, at higher concentrations and more toxic levels than those required to produce aberrations. Slight elevations in sister-chromatid exchange frequencies caused by hyperosmotic medium were found in the presence of toxicity and severe cell cycle delay. Our data on cell growth inhibition suggest that this is the result of increased incorporation of bromodeoxyuridine per cell due to decreased numbers of growing cells, although other mechanisms cannot be ruled out. The observations on chromosome aberrations demonstrate the need for keeping in vitro test conditions in the physiological range, and provide a means for investigation of indirect DNA damage.

Animals↗

Phylogeographic support for horizontal gene transfer involving sympatric bruchid species.

BACKGROUND: We report on the probable horizontal transfer of a mitochondrial gene, cytb, between species of Neotropical bruchid beetles, in a zone where these species are sympatric. The bruchid beetles Acanthoscelides obtectus, A. obvelatus, A. argillaceus and Zabrotes subfasciatus develop on various bean species in Mexico. Whereas A. obtectus and A. obvelatus develop on Phaseolus vulgaris in the Mexican Altiplano, A. argillaceus feeds on P. lunatus in the Pacific coast. The generalist Z. subfasciatus feeds on both bean species, and is sympatric with A. obtectus and A. obvelatus in the Mexican Altiplano, and with A. argillaceus in the Pacific coast. In order to assess the phylogenetic position of these four species, we amplified and sequenced one nuclear (28S rRNA) and two mitochondrial (cytb, COI) genes. RESULTS: Whereas species were well segregated in topologies obtained for COI and 28S rRNA, an unexpected pattern was obtained in the cytb phylogenetic tree. In this tree, individuals from A. obtectus and A. obvelatus, as well as Z. subfasciatus individuals from the Mexican Altiplano, clustered together in a unique little variable monophyletic unit. In contrast, A. argillaceus and Z. subfasciatus individuals from the Pacific coast clustered in two separated clades, identically to the pattern obtained for COI and 28S rRNA. An additional analysis showed that Z. subfasciatus individuals from the Mexican Altiplano also possessed the cytb gene present in individuals of this species from the Pacific coast. Zabrotes subfasciatus individuals from the Mexican Altiplano thus demonstrated two cytb genes, an "original" one and an "infectious" one, showing 25% of nucleotide divergence. The "infectious" cytb gene seems to be under purifying selection and to be expressed in mitochondria. CONCLUSION: The high degree of incongruence of the cytb tree with patterns for other genes is discussed in the light of three hypotheses: experimental contamination, hybridization, and pseudogenisation. However, none of these seem able to explain the patterns observed. A fourth hypothesis, involving recent horizontal gene transfer (HGT) between A. obtectus and A. obvelatus, and from one of these species to Z. subfasciatus in the Mexican Altiplano, seems the only plausible explanation. The HGT between our study species seems to have occurred recently, and only in a zone where the three beetles are sympatric and share common host plants. This suggests that transfer could have been effected by some external vector such as a eukaryotic or viral parasite, which might still host the transferred fragment. REVIEWERS: This article was reviewed by Eric Bapteste, Adam Eyre-Walker and Alexey Kondrashov.

Journal Article↗

Rate of endothelial expansion is controlled by cell:cell adhesion.

Procedures used to alleviate blood vessel occlusion result in varying degrees of damage to the vascular wall and endothelial denudation. The presence of intact, functioning endothelium is thought to be important in controlling smooth muscle cell growth, and limiting the intimal thickening which results from damage to the vessel wall. Recovery of the endothelium is commonly slow and incomplete, due in part to endothelial lateral cell:cell adhesion, which limits cell migration and proliferation. We have investigated the effect of fibroblast growth factor 2 and vascular/endothelial growth factor on the relationship between the temporal distribution of the junctional adhesion proteins, platelet/endothelial cell adhesion molecule, vascular/endothelial cadherin and plakoglobin, and cellular migration and proliferation in an in vitro model of endothelial expansion. We found that whereas cell:cell junctions were initially disturbed to similar extents by single applications of the growth factors, outward cell migration and proliferation rates were inversely correlated with the speed at which cell:cell junctions were re-established. This occurred very rapidly with vascular/endothelial growth factor treatment and more slowly with fibroblast growth factor-2, resulting in more extensive outward migration and proliferation in response to the latter. Platelet/endothelial cell adhesion molecule and vascular/endothelial cadherin appeared to be associated with cell:cell junctional control of migration and proliferation, while plakoglobin did not contribute. It was concluded that the rate of endothelial expansion in response to growth factors, is limited by the rate of re-association of junctional complexes following initial disruption.

Animals↗

Cancer incidence among male pesticide applicators in the Agricultural Health Study cohort exposed to diazinon.

Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.

Adult↗

Potassium and sodium intake and excretion in calcium stone forming patients.

OBJECTIVE: To determine mean potassium (K) intake and its correlation with urinary calcium (uCa) and citrate excretion, as well as uCa, sodium (Na), and K levels of calcium stone forming patients. We determined the K-rich foods most commonly consumed by these patients. DESIGN: Case-control. SETTING: University-affiliated outpatient renal Lithiasis Unit. PATIENTS AND CONTROLS: One hundred hypercalciuric calcium stone forming patients (CSF, 54 men/46 women), 37 with associated hypocitraturia, were sequentially enrolled in the study that was performed before the initiation of any care for their renal stones. The control group consisted of 100 age-matched healthy subjects (HS, 47 men/53 women) who were laboratory employees with no history of renal stones. INTERVENTION: The analyses consisted of a 3-day dietary record to determine the mean K and calcium (Ca) intakes, and a 24-hour urine sample with measurements of K, Ca, Na, and citrate. MAIN OUTCOME MEASURE: K and Na intake determined by dietary record. RESULTS: uCa and Na levels and the Na/K ratio were significantly higher for CSF versus HS (238 +/- 118 v 148 +/- 74 mg/24 hours, 238 +/- 100 v 181 +/- 68 mEq/24 hours, 6.6 +/- 3.5 v 5.1 +/- 2.3, respectively, P < .05). The mean citrate excretion was lower in CSF than in HS patients (410 +/- 265 v 530 +/- 240 mg/24 hours). Mean uCa did not differ between groups. CSF patients showed a higher sodium chloride intake compared with HS (14 +/- 4 vs 8 +/- 3 g/day). The mean Ca intake of CSF and HS were 559 +/- 327 and 457 +/- 363 mg/day, respectively. The mean K intake of CSF and HS were 58 +/- 17 and 51 +/- 27 mEq/day. A positive correlation was observed between uCa and urinary sodium (r = .40 and r = .65, P < .05), urinary potassium and urinary citrate (r = .25 and r = .53, P < .05), uCa and Na/K (r = .33 and r = .56, P < .05) respectively for CSF and HS. The following were the K-rich foods consumed at least once a day by these groups: beans (by 70% of CSF and 75% of HS), tomatoes (by 42% of CSF and 50% of HS), oranges (by 30% of CSF and 55% of HS), and bananas (by 42% of CSF and 23% of HS). CONCLUSION: Despite the consumption of K-rich foods at least once a day, the mean K intake by CSF patients was 58 mEq/day. This intake can still be considered to be low, although it meets recommended daily dietary allowance requirements. Therefore, we describe herein a population of CSF with high-Na intake and normal- to low-K intake, which may contribute to stone formation.

Adult↗

Emergence of highly trimethoprim-sulfamethoxazole-resistant Shigella in a native American population: an epidemiologic study.

Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) emerged among Shigella isolates from the Navajo Reservation in the southwestern United States in 1985, years after this antimicrobial agent came into common use. In the study area, TMP-SMX resistance increased dramatically from 3 per cent in 1983 to 21 per cent in 1985. Resistance was polyclonal and occurred in both S. sonnei and S. flexneri. No single plasmid was common to all resistant strains. However, all 28 TMP-SMX resistant isolates examined were resistant to ampicillin and streptomycin and had minimum inhibitory concentrations to sulfamethoxazole of greater than or equal to 4,096 micrograms/ml and to trimethoprim of greater than or equal to 1,024 micrograms/ml. The authors found that 28 of 101 Navajo children with gastrointestinal symptoms who were not taking antimicrobials had TMP-SMX-resistant aerobic fecal flora. To determine risk factors for acquiring resistant strains, they compared 40 case-patients with TMP-SMX-resistant Shigella to 66 controls with TMP-SMX-sensitive Shigella. Case-patients were more likely than controls to have used antimicrobials recently (p = 0.004) and to be hospitalized for shigellosis (p = 0.05). These findings suggest that polyclonal highly TMP-SMX-resistant Shigella emerged by transfer of trimethoprim resistance genes from aerobic bowel flora to endemic Shigella strains, that use of antimicrobials can lead to symptomatic shigellosis and thus the persistence of trimethoprim-resistant Shigella, and that appropriate therapy of shigellosis on the reservation is now a major challenge.

Adolescent↗

Animal farming and the oral microbiome in the Agricultural Health Study.

BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study. METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption). RESULTS: Overall, 63&#xa0;% of participants raised farm animals, most commonly cattle (46&#xa0;%) and hogs (20&#xa0;%). Those who raised a large number of hogs (&#x2265;2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry). CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.

Microbiota↗

Craniosynostosis in transgenic mice overexpressing Nell-1.

Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS), one of the most common congenital craniofacial deformities. Here we describe the creation and analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals exhibited CS-like phenotypes that ranged from simple to compound synostoses. Histologically, the osteogenic fronts of abnormally closing/closed sutures in these animals revealed calvarial overgrowth and overlap along with increased osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies were restricted to calvarial bone, despite generalized, non-tissue-specific overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial osteoblast differentiation and mineralization under normal culture conditions. Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline phosphatase expression and micronodule formation. Conversely, downregulation of Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1 overexpression induced calvarial overgrowth resulting in premature suture closure in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps as part of a complex chain of events resulting in premature suture closure. On a cellular level, Nell-1 expression may modulate and be both sufficient and required for osteoblast differentiation.

Adenoviridae↗

Modified step-up protein feeding regimens for egg-type chickens. 1. Growth and production performance.

Effects of sequential changes in dietary protein on growth from 0 to 20 weeks of age and on egg production from 20 to 72 weeks of age were evaluated with White Leghorn chickens. Four dietary treatments were compared. They consisted of three dietary regimens wherein an 18% crude protein (CP) diet was fed to 1, 2, or 3 weeks of age (Treatments 1, 2, and 3, respectively) and then common 12, 15, and 18% CP diets to 8, 14, and 20 weeks, respectively. These three regimens were compared with a control regimen (Treatment 4) that consisted of feeding 18, 15, and 12% CP diets to 6, 14, and 20 weeks of age, respectively. At 20 weeks of age, 144 birds from each treatment were moved into laying cages for the subsequent 52 weeks of egg production. In comparison with birds on the control feeding regimen, those reared under Treatments 1, 2, and 3 consumed significantly less feed during the 20-week growing period. Birds of Treatments 2 and 3 consumed significantly more protein than those of Treatments 1 and 4. By feeding a 12% CP diet from 1, 2, and 3 to 8 weeks of age, body weights were significantly lower than the average body weight of the control birds, approximately 20, 17, and 13%, respectively, by 6 weeks of age, but only 2 to 4% at 16 weeks of age, and by nonsignificant amounts at 28 weeks of age. Treatment 1 birds consumed 1.8% (significantly) less feed per unit body weight and were 2.6% (significantly) lighter at 20 weeks of age compared with the control birds.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗