Impact of the Delaney Clause in the EPA

The U.S. Environmental Protection Agency serves as the lead agency of the Federal government for the regulation of pesticide use in the United States. Regulatory responsibilities are mandated in the Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and several sections of the Federal Food Drug and Cosmetic Act (FFDCA). In order for a pesticide to be used in the U.S., it must either be granted a full registration under Section 3, or offered special consideration under Section 18 or 24 of FIFRA. Tolerances (maximum allowable residue limits) for pesticides to be used on agricultural commodities meant for human consumption or animal feed are established under Sections 408 and/or 409 of FFDCA. This presentation will describe the underlying conflict between Section 409 of FFDCA and both Section 408 and FIFRA, the recommendations made by the National Academy of Sciences in its 1987 publication Regulating Pesticides in Food--The Delaney Paradox, EPA's attempts to implement these recommendations, the true impact of "Delaney" on the ability of EPA to grant tolerances on raw or processed foods for chemicals determined to meet the "induce cancer" criterion and the status of legislation designed to "fix" Delaney.     

Nasal lavage as tool for health effect assessment of photochemical air pollution

In order to achieve esthetically more satisfying results, it has been proposed to place ITI implants with their border between the rough and smooth surfaces below the level of the alveolar crest, thereby obtaining a submucosally located implant shoulder following healing. The aim of the present experimental study was to clinically and radiographically evaluate the tissue response to the placement of one-stage transmucosal implants with the border between the rough and the smooth surfaces sunk by 1 mm into a subcrestal location. 11 patients underwent comprehensive dental care including the placement of 2 implants of the ITI Dental Implant System in the same quadrant (test and control). Randomly assigned control implants were placed according to the manufacturer's instructions, i.e. the border between the rough titanium plasma-sprayed and the smooth polished surfaces precisely at the alveolar crest. At the test implant the apical border of the polished surface was placed approximately 1 mm below the alveolar crest. Probing bone levels were assessed at implant placement (baseline), 4 and 12 months later. Modified plaque and modified gingival indices were recorded at 1, 2, 3, 4 and 12 months. Clinical probing depth and "attachment" levels were measured at 4 and 12 months. All parameters were assessed at 6 sites around each implant. The mean for each implant was calculated and used for analysis. The Wilcoxon matched pairs signed rank test and the Student t-test were applied to detect differences over time and between the test and control implants. At baseline, a mean difference in probing bone level of -0.86 mm (SD 0.43 mm, p < 0.05) was found between test and control implants with the test implants being placed more deeply. Both test and control implants lost a significant amount of clinical bone height during the first 4 months (test 1.16 mm, p < 0.05; control 0.58 mm, p < 0.05). However, only the test implants significantly lost clinical bone height from 4-12 months (test 1.04 mm, p < 0.05; control 0.45 mm, p = 0.08). Overall, the test implants lost 2.26 mm and the control implants 1.02 mm of bone height during the first year of service. On the average, the test implants demonstrated a bone level of 0.38 mm lower than the controls at 12 months. Except for the modified gingival index at 4 months (mean difference 0.21, SD 0.19, p < 0.05), no clinical parameters yielded significant differences between test and control implants at any time. It is concluded that in addition to the crestal bone resorption occurring at implants placed under standard conditions, the bone adjacent to the polished surface of more deeply placed ITI implants is also lost over time. From a biological point of view, the placement of the border between the rough and the smooth surfaces into a subcrestal location should not be recommended.     

Molecular lipophilicity potential (MLP) in drug design. Complementing theoretical tools with experimental results

The Molecular Lipophilicity Potential (MLP) is a versatile tool in drug design whose present state and potential developments are reviewed here. The MLP offers a three-dimensional representation of lipophilicity as calculated from partition coefficients. The intermolecular recognition forces and intramolecular effects encoded in lipophilicity are presented, followed by the theoretical foundations and validation of the MLP. It is then demonstrated that the MLP allows for the first time to investigate the dependence of lipophilicity on conformation. As a matter of fact, the MLP combined with an exploration of the conformational space of a solute reveals its "chameleonic" behaviour, i.e. its capacity to adapt to the molecular environment. Other applications of the MLP are presented and illustrated, namely its integration into 3D-QSAR (Comparative Molecular Field Analysis, CoMFA) and its interest as a docking tool.     

Acetogenic coccoid spore-forming bacteria isolated from the rumen

Thirteen strains of a new acetogenic bacterium were isolated from the rumen contents of lambs, llamas and bisons. This paper is the first report of Gram-positive coccoid spore-forming bacteria occurring in chains and able to use H2 + CO2 as energy source and produce acetate from this gas mixture. One of them, chosen as the reference strain for its efficiency in utilizing H2/CO2 likely via the acetyl-CoA pathway, was characterized in detail. The G + C ratio of the DNA of the organism was 46.5 mol%. The temperature and pH optimum were 37 degrees-40 degrees C and 6.3-6.8, respectively. Numerous organic substrates including some o-methylate aromatic compounds were used heterotrophically. The full 16S rRNA gene sequence was determined. The phylogeny, physiology, morphology and numerous features described here are sufficiently different from those of any bacteria described today to justify the definition of a new species. The name "New acetogenic bacterium" is temporarily proposed, awaiting a future taxonomic revision of the genus Clostridium.     

The role of arterial hypertension in the occurrence of strokes at a young age

The analysis of insult occurrence in patients at the age under 45 years, caused by blood hypertension, shows, that they make 30.1% from common number of insult in 166 young people, treated in the neurological and other departments of Burdenko Main Military Clinical Hospital in 1989-1996. On occasion of ischemic insult were treated 37 patients, hemorrhagic--13. The reason of insults was "soft" blood hypertension: in 51.4%--at ischemic insult and in 30.1%--hemorrhagic. The authors consider, that the main direction of prophylaxis of insult is active revealing and adequate treatment of the patients with blood, including "soft" hypertension, use of hypotensive preparations and some non-medicative methods of treatment.     

The role of the Cell Saver autologous transfusion method in preventing the pulmonary distress syndrome during open-heart operations on children

Complex estimation of the state of the lungs at the postperfusion and early postoperative periods based on roentgenological, clinical data, investigations of the parameters of oxygenation and mechanics of respiration was carried out in 32 children with septal defects of the heart, operated upon under conditions of artificial blood circulation with different kinds of the transfusion maintenance including the apparatus "Cell Saver 5" (CS) for the reinfusion of autoerythrocytes. The dynamics of endotoxicosis, hematological parameters during and after operation and requirements in transfusion media were studied. Differences in these indicators were established between the patients operated upon with the use of donor hemocomponents and those who were operated upon with CS. It allowed a conclusion about the role of the method of intraoperative reinfusion of erythrocytes in substantially less frequency and severity of the postperfusional pulmonary complications in this category of patients.     

Distinct immunological states in murine cutaneous leishmaniasis by immunising with different amounts of antigen: the generation of beneficial, potentially harmful, harmful and potentially extremely harmful states

Infection of BALB/c mice with a standard and substantial number of Leishmania major parasites results in progressive disease, following the induction of a parasite-specific Th2 response. These mice have been designated as "susceptible" on this basis. We show that distinct types of immune response can be generated in "susceptible" BALB/c mice depending upon the number of parasites employed for infection, and that the pathophysiological consequences of such distinct responses are dramatically different. Infection with very low numbers of parasites results in the exclusive induction of a cell-mediated, Th1 response, and the generation of resistance to the standard and substantial challenge. Spleen cells from such resistant mice can confer resistance upon normal mice when transferred to them, but these spleen cells do not contain T cells expressing DTH or Th1 effector cells that produce IFN gamma on short term culture (48 hrs) with parasite antigen. The immune response in this case appears to result in the virtual elimination of parasites from the lymph node draining the site of infection and, by implication, from the infected mouse. We suggest that such elimination results in the absence of antigen stimulation and hence of effector T cells, and that "memory Th1 cells" are responsible for the capacity of spleen cells to confer resistance on normal mice. We predict such mice will not suffer parasitemia upon immune suppression, i.e. are not susceptible to reactivation disease. This is the "beneficial state". In contrast to this infection with a very low number of parasites infection with a low number usually results in one of two states: (i) The generation of a response with a very small Th2 component, production of a small amount of antibody, chronic parasitemia and hence chronic generation of parasite-specific effector Th1/Th2 cells, or (ii) The generation of a response with a greater Th2 component, the production of more antibody, the formation of a frank lesion, and the long term generation of a stable, mixed Th1/Th2 response. We refer to the latter state as borderline leishmaniasis in analogy with borderline leprosy. Parasites can be recovered from the draining lymph node in both these cases many months after infection. We therefore believe that mice infected with a low number of parasites, that harbour a chronic subclinical infection, will suffer reactivation disease upon immune suppression, and we consequently designate the state generated as potentially harmful. We consider mice with borderline disease to be in a harmful state. Mice immunised with high doses of parasite antigen produce in the long term Th2 responses, whereas those immunised with lower doses produce Th1 responses. Mice immunised to produce a Th2 response were subsequently infected with a very low number of parasites that is normally contained. The generation of a Th2 response results in the generation of a Th2 imprint, such that the response to the low dose infection is modulated from a Th1 to a Th2 mode, resulting in progressive disease. We argue that immunisation/vaccination, resulting in a state that deviates the protective response to a non-protective mode, may result in epidemics. Such a state has the potential for being extremely harmful.     

Brick by brick computation of the gibbs free energy of reaction in solution using quantum chemistry and COSMO‐RS

The computational modeling of reactions is simple in theory but can be quite tricky in practice. This article aims at the purpose of providing an assistance to a proper way of describing reactions theoretically and provides rough guidelines to the computational methods involved. Reactions in liquid phase chemical equilibrium can be described theoretically in terms of the Gibbs free energy of reaction. This property can be divided into a sum of three disjunct terms, namely the gas phase reaction energy, the finite temperature contribution to the Gibbs free energy, and the Gibbs free energy of solvation. The three contributions to the Gibbs free energy of reaction can be computed separately, using different theoretico‐chemical calculation methods. While some of these terms can be obtained reliably by computationally cheap methods, for others a high level of theory is required to obtain predictions of quantitative quality. To propose workflows which can strike the balance between accuracy and computational cost, a number of benchmarks assessing the precision of different levels of theory is given. As an illustrative example, the low‐temperature hydrogenation reaction of acetaldehyde to ethanol in solvent toluene is shown. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3944–3954, 2017     

In support of the telomere concept

The frequency of recovered X-ray-induced (4000R) rearrangements that, in all probability mimic terminal deletions of the X chromosome was only one of, roughly, 10-5 X chromosomes screened for tip deficiencies. Although the single exception looks terminally deleted, it is probably capped by a very short or nonpolytene telomeric segment. It is apparent from these data that the probability of "healing" or stabilization of a terminally deleted X in the zygotic nucleus or developing embryo of Drosophila melanogaster is vanishingly small. The telomeric caps in two obviously interstitial deficiencies that were recovered represent, roughly, 1/500 of the length of a mitotic chromosome. These findings give some indication of the extreme difficulty of detecting short telomeric segments capping either deleted polytene chromosomes or deleted metaphase chromosomes of, for example, humans.