Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

Development of Multiwell-Plate Methods Using Pure Cultures of Methanogens To Identify New Inhibitors for Suppressing Ruminant Methane Emissions.

Hydrogenotrophic methanogens typically require strictly anaerobic culturing conditions in glass tubes with overpressures of H2 and CO2 that are both time-consuming and costly. To increase the throughput for screening chemical compound libraries, 96-well microtiter plate methods for the growth of a marine (environmental) methanogen Methanococcus maripaludis strain S2 and the rumen methanogen Methanobrevibacter species AbM4 were developed. A number of key parameters (inoculum size, reducing agents for medium preparation, assay duration, inhibitor solvents, and culture volume) were optimized to achieve robust and reproducible growth in a high-throughput microtiter plate format. The method was validated using published methanogen inhibitors and statistically assessed for sensitivity and reproducibility. The Sigma-Aldrich LOPAC library containing 1,280 pharmacologically active compounds and an in-house natural product library (120 compounds) were screened against M. maripaludis as a proof of utility. This screen identified a number of bioactive compounds, and MIC values were confirmed for some of them against M. maripaludis and M. AbM4. The developed method provides a significant increase in throughput for screening compound libraries and can now be used to screen larger compound libraries to discover novel methanogen-specific inhibitors for the mitigation of ruminant methane emissions.IMPORTANCE Methane emissions from ruminants are a significant contributor to global greenhouse gas emissions, and new technologies are required to control emissions in the agriculture technology (agritech) sector. The discovery of small-molecule inhibitors of methanogens using high-throughput phenotypic (growth) screening against compound libraries (synthetic and natural products) is an attractive avenue. However, phenotypic inhibitor screening is currently hindered by our inability to grow methanogens in a high-throughput format. We have developed, optimized, and validated a high-throughput 96-well microtiter plate assay for growing environmental and rumen methanogens. Using this platform, we identified several new inhibitors of methanogen growth, demonstrating the utility of this approach to fast track the development of methanogen-specific inhibitors for controlling ruminant methane emissions.

Fibromyalgia and bipolar disorder: extent of comorbidity and therapeutic implications.

Fibromyalgia (FM) is a syndrome that affects muscles and soft tissues. Presenting symptoms include chronic muscle pain, fatigue, sleep problems and psychological symptoms, including depression and anxiety. There exists strong evidence of a comorbidity between FM and Bipolar Disorder (BD). In this study, papers from 2006 to February 2016 that examined the comorbidity and etiological similarities of FM and BD were reviewed, as well as the therapeutic implications of these findings. The reviewed articles showed that an adequate psychiatric screening for BD is recommended in FM patients with depressive symptoms, in order to decrease administration of antidepressants for BD, due to the lack of proven efficacy, and to limit antidepressant-induced mania. Alternative therapies, such as agomelatine, memantine and psychotherapic treatment should be considered.

Binaural fusion and listening effort in children who use bilateral cochlear implants: a psychoacoustic and pupillometric study.

Bilateral cochlear implants aim to provide hearing to both ears for children who are deaf and promote binaural/spatial hearing. Benefits are limited by mismatched devices and unilaterally-driven development which could compromise the normal integration of left and right ear input. We thus asked whether children hear a fused image (ie. 1 vs 2 sounds) from their bilateral implants and if this "binaural fusion" reduces listening effort. Binaural fusion was assessed by asking 25 deaf children with cochlear implants and 24 peers with normal hearing whether they heard one or two sounds when listening to bilaterally presented acoustic click-trains/electric pulses (250 Hz trains of 36 ms presented at 1 Hz). Reaction times and pupillary changes were recorded simultaneously to measure listening effort. Bilaterally implanted children heard one image of bilateral input less frequently than normal hearing peers, particularly when intensity levels on each side were balanced. Binaural fusion declined as brainstem asymmetries increased and age at implantation decreased. Children implanted later had access to acoustic input prior to implantation due to progressive deterioration of hearing. Increases in both pupil diameter and reaction time occurred as perception of binaural fusion decreased. Results indicate that, without binaural level cues, children have difficulty fusing input from their bilateral implants to perceive one sound which costs them increased listening effort. Brainstem asymmetries exacerbate this issue. By contrast, later implantation, reflecting longer access to bilateral acoustic hearing, may have supported development of auditory pathways underlying binaural fusion. Improved integration of bilateral cochlear implant signals for children is required to improve their binaural hearing.

Psychosocial-immune relationships in HIV disease.

Human immunodeficiency virus (HIV) is now commonly viewed as a chronic disease, which often consists of a wide array of recurrent and sometimes severe psychosocial stressors. An individual's response to these multiple challenges over time may impact their health. In this article, we review research examining the relationship of psychologic factors (eg, depression, stressful life events, coping, social support) with immune system function and disease course. We also explore some of the potential physiologic pathways that may underlie these types of psychosocial-immune relationships, as well as the effects of psychologic interventions, particularly cognitive-behavioral stress management (CBSM), on the psychosocial, neuroendocrine, and immune functioning of people living with HIV. We conclude by suggesting some areas for future research, particularly the study of HIV-positive women.

Predilection for frailty remedial strategies among black and white seniors.

BACKGROUND: Frailty prevention and remedial programs based on exercise, hormone replacement, and vitamin supplementation are becoming available for use with older patients, but success of these programs depends largely on seniors' willingness to participate. METHODS: We evaluated preferences for specific aspects of these programs using a sample of 359 older persons recruited from potential delivery sites. Main effects and subgroup analyses were done. RESULTS: Subjects preferred stretching, chair-based, walking, and dynamic balance exercises over lifting weights, dancing, hormone and vitamin therapy; exercising alone in their own homes over exercising in groups; and vitamins over hormones. Preferences were affected to some extent by sex, race, recruitment site, and functional status. However, subjects' willingness even to consider exercise was rarely as high as the desired levels of participation set forth in Healthy People 2000. CONCLUSIONS: Physicians and public health authorities need to educate older persons about effective methods to prevent or treat frailty.

Effect of soybean hulls, soy lecithin, and soapstock mixtures on ruminal fermentation and milk composition in dairy cows.

Two experiments were conducted to determine effects of soybean hulls, soy lecithin, and soapstock mixtures on ruminal fermentation, milk composition, and ruminal microbial populations. In Experiment 1, 20 Holstein dairy cows were assigned to one of five total mixed rations (TMR) in replicated 5 x 5 Latin squares to measure the effect of TMR on intake and milk composition. Four ruminally fistulated cows were used in a 4 x 5 Youden square to measure the effect of TMR on ruminal fermentation. The TMR consisted of 40 or 50% alfalfa and corn silages, 13% soybean hulls, and 47 or 37% of a concentrate containing either 2.25% soybean oil; 2.25% lipid from a mixture of soybean hulls, soy lecithin, and soapstock; or no added lipid. The ratios of soy lecithin to soapstock evaluated were 1:1, 2.5:1, and 4:1 (dry basis). The TMR containing soy lecithin and soapstock at ratios of 1:1 and 2.5:1 resulted in higher milk C18:2 than did the soybean oil TMR. Rate of ruminal NDF digestion of soybean hulls was reduced for the soybean oil TMR. In Experiment 2, a semi-continuous culture system was used to determine effects of soybean oil or an optimal mixture of soy lecithin and soapstock (1:1, wt/wt) on fermentation of soybean hulls and microbial populations. The TMR containing the lipid mixture increased the ratio of acetate to propionate compared with the TMR containing soybean oil and resulted in higher total protozoal counts than did the control TMR. The TMR containing mixtures of soy lecithin and soapstock at ratios of 1:1 and 2.5:1 elevated milk C18:2, and no negative effect on NDF digestion was detected, indicating some degree of ruminal protection.

Integrating the physician into the organization decision-making process.

Physicians need to be involved in organizational decision making, and institutional goals are achieved through the integration of operational quality committees.

Effects of hydroxyethyl starch after trauma-hemorrhagic shock: restoration of macrophage integrity and prevention of increased circulating interleukin-6 levels.

OBJECTIVES: To determine the effects of resuscitation with the colloidal solution (hydroxyethyl starch) vs. crystalloid solution on cell-mediated immune functions after trauma-hemorrhage. DESIGN: Prospective, multiexperimental, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Thirty-six inbred male C3H/HEN (endotoxin-sensitive) mice, aged 6 to 7 wks, and weighing 18 to 23 g. INTERVENTIONS: Crystalloid (lactated Ringer's solution) with and without 6% hydroxyethyl starch after trauma-hemorrhage. MEASUREMENTS AND MAIN RESULTS: Mice underwent laparotomy, were bled to and maintained at a blood pressure of 40 mm Hg for 60 mins, then resuscitated with either 4x the shed blood volume as lactated Ringer's solution or 2x the shed blood volume as lactated Ringer's solution plus 1 x 6% hydroxyethyl starch. Sham mice were neither hemorrhaged nor resuscitated. At 2 or 24 hrs posthemorrhage, serum, splenocytes, peritoneal macrophages, and splenic macrophages were obtained. Bioassays were used to determine interleukin-2, interleukin-3, and interleukin-6 concentrations, while splenocyte proliferation was assessed by 3H-thymidine incorporation. Trauma-hemorrhage markedly depressed splenocyte proliferation, interleukin-6 release by macrophages, and lymphokine release at 2 and 24 hrs postresuscitation. The combination of lactated Ringer's solution and hydroxyethyl starch neither restored, nor exacerbated lymphocyte functions. Interleukin-6 release by peritoneal macrophages was restored 24 hrs after hydroxyethyl starch infusion; serum interleukin-6 concentrations remained at sham levels. CONCLUSIONS: Since the use of lactated Ringer's solution and hydroxyethyl starch after hemorrhage did not adversely affect cell-mediated immune functions, but produced salutary effects on macrophage functions, hydroxyethyl starch is a safe and beneficial resuscitation adjunct.

Modulation of macrophage membrane phospholipids by n-3 polyunsaturated fatty acids increases interleukin 1 release and prevents suppression of cellular immunity following hemorrhagic shock.

Studies have suggested that the significant suppression of cellular immunity following hemorrhage may be due to an increased release of prostaglandin E2 (PGE2) by macrophages. Since diets high in n-3 polyunsaturated fatty acids decrease PGE2 synthesis, we assessed whether hemorrhage-induced immunosuppression could be prevented by dietary manipulation. C3H/HeN mice were fed for 3 weeks with fat sources derived from corn oil, safflower oil, or fish oil, then bled to a mean blood pressure of 35 mm Hg maintained for 60 minutes. Following this, the animals were adequately resuscitated with fluids and killed 24 hours later. In the corn oil and safflower oil groups, hemorrhage resulted in a significant increase in PGE2 release by peritoneal macrophages, a marked suppression of peritoneal macrophage antigen presentation capacity, interleukin 1 release, splenocyte proliferation, and interleukin 2 secretion compared with shams. However, feeding mice with fish oil for 3 weeks prior to hemorrhage prevented the rise in PGE2 release and maintained normal macrophage and splenocyte functions following hemorrhage. Thus, the elevated release of PGE2 by peritoneal macrophages plays a pivotal role in hemorrhage-induced immunosuppression. Moreover, diets high in n-3 polyunsaturated fatty acids may offer a new therapeutic approach for preventing posthemorrhage immunosuppression and increased mortality from sepsis.

Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis.

We examined whether (1) there is an association between elevated circulating levels of transforming growth factor-beta (TGF-beta) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-beta release) or TGF-beta could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-beta value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-beta (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-beta at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-beta, thereby attenuating host immunosuppression during sepsis.

Aerobiology of the Colorado Rockies: pollen count comparisons between Vail and Denver, Colorado.

Pollen patterns were compared between Vail, CO (8,200 feet elevation), Aspen, CO (7,900 feet) and Denver, CO (5,280 feet) from 1984 through 1988. Counts were obtained at all sites with a volumetric intermittent cycling rotating impaction sampler. Aspen and Denver were compared in 1984, and Vail and Denver from 1985 through 1988. While counts were generally lower in the mountain sites than Denver, certain pollens, especially trees, were quite high. Ragweed was essentially absent from Aspen and Vail, and chenopod-amaranth counts were very low. Cedar, pine, and aspen frequently pollinated despite active snowfall.

Attempts to immunoprecipitate the LHRH precursor synthesized in cell free systems.

In order to determine the molecular weight of the Luteinizing Hormone Releasing Hormone (LHRH) precursor, poly(A)-RNA from rat hypothalami and human placenta were translated in two mRNA dependent cell free translation systems. Total translation products were immunoprecipitated with two antisera that recognized LHRH high molecular weight forms. After SDS-polyacrylamide slab gel electrophoretic analysis of the immunoprecipitated material and fluorography, we detected in both tissues a protein of 50,000 daltons with the No. 1076 antiserum. This peptide was not immunoprecipitated by the No. 743 anti-LHRH antiserum or by non-immune rabbit serum. However, this protein was not displaced by excess LHRH added during the immunoprecipitation and seemed to be present in species where LHRH has not been reported. These data demonstrated that the LHRH mRNA is present in very low amounts in hypothalamus or placenta and that the sensitivity of the assay is not high enough to recognize it.

Naloxone suppresses food/water consumption in the deprived cat.

Intraperitoneal administration of the opiate antagonist, naloxone hydrochloride, resulted in decreased food and water consumption in drug-naive cats. In a cross-over Latin Square design, food consumed by six cats in a one hour period following 23 hours of deprivation, was decreased significantly below control (p less than 0.05) in linear relation to increasing dose (1 mg/kg and 10 mg/kg) of naloxone. Non-linear and time/order effects were not significant. Water consumption was decreased below control in a linear relation to increasing dose (1 and 10 mg/kg) for 5 of 6 cats at the 0.05 significance level. Non-linear and time/order effects on water consumption were not statistically significant for the same 5 cats. These results, and behavioral signs (i.e., vomiting, persistant vocalization, heavy salivation, mydriasis, moderate catatonia, and hissing) occasionally exhibited by four of the six cats in a 1-hr period following injection of the high dose, suggest a malaise-effect of naloxone.

Influence of a nutrition education program (EFNEP) on infant nutrition in East Harlem.

An assessment of the effectiveness of aides working in the Expanded Food and Nutrition Education Program (EFNEP) to improve the nutritional status of infants was conducted with a group of 118 infants attending a well-baby clinic in a low-income area of New York City. In addition to clinic care, the fifty-seven study infants received home visits from a nutrition aide whose role was to reinforce nutritional advice received at the clinic. The sixty-one control infants received only regular clinic care. The benefits of having an aide were suggested by three observations: Reduction in the practice of introducing whole cow's milk to young infants, familiarizing older infants with a variety of foods, and reducing the prevalence of iron-deficiency anemia. Few of the differences between study and control infants achieved statistical significance, although trends consistently indicated that the presence of aides was beneficial. The problems of assessing the effectiveness of nutrition education programs with healthy infants are discussed.

Infant feeding practices in East Harlem.

Infant feeding practices among low-income infants in East Harlem were surveyed prior to undertaking a nutrition education program. Data were obtained from 24-hr. recalls on 153 infants seen in a well-baby clinic. Intakes of energy, protein, fat, ascorbic acid, iron, and sodium showed wide variations among infants of similar ages. Nutrient intakes were similar for black and Puerto Rican infants, although some ethnic differences were observed in the types of milk and solid foods consumed. Black infants received formula for a longer period, while Puerto Rican infants were transferred to whole cow's milk at a younger age. In contrast black infants were introduced to table foods earlier.

Effect of metabolic state on phytohemagglutinin-P agglutination of normal human erythrocytes.

A reproducible quantitative assay for the lectin-mediated agglutination of human erythrocytes, depending on different rates of settling of agglutinated and nonagglutinated erythrocytes, was developed. This assay was used to study the aggregation of human erythrocytes by phytohemagglutinin-P. The aggregation of human erythrocytes by phytohemagglutinin-P was found to depend upon the metabolic state of the cells. Metabolically depleted erythrocytes agglutinated much less readily than did similar cells supplied with adenosine. This was not due to swelling and rigidity of the cells, since erythrocytes in hypotonic solution did not exhibit significantly altered phytohemagglutinin-P agglutination. Metabolically depleted erythrocytes, or erythrocytes from blood stored 8 weeks, lysed and resealed in the presence of ATP, were agglutinated by phytohemagglutinin-P to a much greater extent than control samples without ATP. The presence of Mg2+, either alone or with ATP, had little effect on the agglutinability of the resealed membranes. Low concentrations of Ca2+ (0.2 mM) had little effect on agglutinability, although high Ca2+ (5 mM) inhibited agglutinability of the resealed membranes somewhat. Both metabolically depleted erythrocytes and depleted erythrocytes, previously treated with adenosine, when treated with trypsin released similar amounts of sialic acid. The agglutinability of the trypsinized adenosine-supplemented cells increased more readily than did that of trypsinized metabolically depleted cells. The agglutination of erythrocytes was not affected by cytochalasin B (40 mug/ml). Vinblastine (0.2 mM) caused depleted erythrocytes to agglutinate similarly to adenosine-supplemented erythrocytes, but had no effect on the agglutination of adenosine-supplemented erythrocytes. It is concluded that ATP in the human erythrocyte probably participates in the modulation of phytohemagglutinin-P agglutinability. This is not a consequence of the more rigid membrane known to accompany ATP depletion in the erythrocyte, or of the effect of ATP levels on Ca2+ or Mg2+ content. It appears likely that ATP modulates human erythrocyte phytohemagglutinin-P agglutinability through interaction, direct or indirect, with a membrane-associated component, which might also be sensitivie to vinblastine.