Oral periopathogens and systemic effects

Management of oral biofilms allows dentists to help control the pathogens responsible for periodontal disease and decay. Increasing evidence indicates that the oral system is a portal for pathogenic microorganisms. This is a cumulative situation with systemic effects that can overcome an individual's resistance threshold, culminating in systemic sequela. New evidence indicates that controlling these oral pathogens has systemic benefits, as oral pathology is related to cardiovascular and respiratory disease, diabetes, and systemic inflammatory responses, as well as low birth weight and pre-term deliveries. Some insurance companies now cover periodontal scaling for gingivitis and periodontal disease for pregnant women and patients at risk for pregnancy.     

On-line computer estimation of carbon dioxide response curves

Anesthesiologists are concerned with the effect of various anesthetics on a patient's central nervous ventilatory control. The most widely accepted method of determining the effect of a drug is to compare carbon dioxide response curves ( e/PetCO₂, where e = minute ventilation [in L/min] andPetCO₂ = end-tidal carbon dioxide [in mm Hg]) measured before and after administration of the drug. Additional information concerning neuromechanical control can be obtained by also including a measure of the airway occlusion pressure (generally measured 100 ms after occlusion, i.e., P₁₀₀).To facilitate these measurements we have developed a portable, computer-controlled data acquisition system. It includes an Apple II+ computer and measures e,PetCO₂, and P₁₀₀. Each subject rebreathes exhaled carbon dioxide through a two-way breathing valve attached to a 9-liter reservoir, which is initially filled with 5% carbon dioxide and balance oxygen. Exhaled carbon dioxide concentrations are measured with an infrared medical gas analyzer on samples taken through a catheter connected at the mouthpiece. The exhaled flow is measured with a pneumotachograph in conjunction with a differential pressure transducer, and P₁₀₀ is determined with a Validyne MP45 pressure transducer.     

Structural Optimization of Indole Derivatives Acting at Colchicine Binding Site as Potential Anticancer Agents

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Fifty million years of beetle evolution along the Antarctic Polar Front

Global cooling and glacial–interglacial cycles since Antarctica’s isolation have been responsible for the diversification of the region’s marine fauna. By contrast, these same Earth system processes are thought to have played little role terrestrially, other than driving widespread extinctions. Here, we show that on islands along the Antarctic Polar Front, paleoclimatic processes have been key to diversification of one of the world’s most geographically isolated and unique groups of herbivorous beetles—Ectemnorhinini weevils. Combining phylogenomic, phylogenetic, and phylogeographic approaches, we demonstrate that these weevils colonized the sub-Antarctic islands from Africa at least 50 Ma ago and repeatedly dispersed among them. As the climate cooled from the mid-Miocene, diversification of the beetles accelerated, resulting in two species-rich clades. One of these clades specialized to feed on cryptogams, typical of the polar habitats that came to prevail under Miocene conditions yet remarkable as a food source for any beetle. This clade’s most unusual representative is a marine weevil currently undergoing further speciation. The other clade retained the more common weevil habit of feeding on angiosperms, which likely survived glaciation in isolated refugia. Diversification of Ectemnorhinini weevils occurred in synchrony with many other Antarctic radiations, including penguins and notothenioid fishes, and coincided with major environmental changes. Our results thus indicate that geo-climatically driven diversification has progressed similarly for Antarctic marine and terrestrial organisms since the Miocene, potentially constituting a general biodiversity paradigm that should be sought broadly for the region’s taxa.

Antarctica’s isolation, cooling, and glacial–interglacial cycles over the Cenozoic have resulted in the remarkable diversification of a unique marine fauna (1, 2). The investigation of marine radiations in Antarctica has reshaped modern understanding of biodiversity processes, for example, by revealing a surprising inverse latitudinal gradient in diversification rates for fish and brittle stars (3–5). In contrast, Antarctica’s paleoclimatic legacy for terrestrial communities has long been considered one of widespread extinction due to glaciation. Evidence of terrestrial species surviving in Antarctic glacial refugia (6) and discoveries of substantial endemic diversity and biogeographic structuring in some groups (7, 8) is changing this narrative, indicating extended evolutionary histories on land. Yet, such evolutionary histories remain obscured by a lack of large-scale molecular phylogenetic work, with most Antarctic terrestrial research focused on small subsets of species or populations (9, 10). The few studies that have taken a multilocus phylogenetic approach have uncovered hidden terrestrial diversity and signals of long-term allopatric divergence (e.g., refs. 11 and 12), hinting that Cenozoic climatic processes may have driven terrestrial diversification in ways similar to that for marine life.The hypothesis that diversification has proceeded similarly in Antarctic marine and terrestrial groups has not been tested. While the extinction of a diverse continental Antarctic biota is well established (13), mounting evidence of significant and biogeographically structured Antarctic terrestrial diversity (8, 14, 15) with a long evolutionary history (6, 16) suggests the possibility of broadly similar diversification processes across marine and terrestrial Antarctic systems. If valid for some taxa, further tests should then be sought across a wider variety of organisms. Here, we therefore evaluate the terrestrial applicability of the paradigm emerging for Antarctic marine biodiversity—that a major cooling phase from the mid-Miocene climatic transition (14 Ma) onwards, and subsequent habitat restructuring, have led to significant and ongoing diversification for many taxa, including those with much older origins in the region (2, 4, 17). We do so by using one of the most well-known and speciose groups from the sub-Antarctic, the herbivorous Ectemnorhinini weevils (Coleoptera: Curculionidae) (18–20).Preliminary molecular studies indicate that the Ectemnorhinini, along with numerous other terrestrial taxa, have long histories in the sub-Antarctic, extending to the Miocene or earlier [e.g., beetles (21), midges (22), and springtails (11)]. This enables a comparison of their evolution throughout the same periods of environmental change that drove the diversification of Antarctic marine taxa. Moreover, the sub-Antarctic islands overlap spatially with the Southern Ocean, with climates that reflect oceanic conditions both past and present (23, 24). While in some respects quite different to the continental Antarctic, the islands are in other ways quite similar, providing a window into diversification processes that might be sought for continental groups, especially given their age and biogeographic structuring. Both regions share many higher taxa (e.g., ref. 25), a dynamic geo-climatic history (6, 26), a profound degree of isolation, and indications that climatic events likely structured their biota (6, 8, 27). The terrestrial habitat on the continent and its surrounding islands is fragmented by large expanses of ice or ocean, respectively, and has been further isolated by the Antarctic Circumpolar Current for at least 34 Ma (28, 29). Cyclic growth and contraction of ice sheets throughout the Plio–Pleistocene, though typically associated with the continent, has also had extensive impacts on the sub-Antarctic islands (26). The more intensively surveyed sub-Antarctic faunas thus provide an opportunity to investigate terrestrial diversification processes for the wider Antarctic while recognizing that for many groups on the continent, the main legacy of change has been extinction.To test the hypothesis that a major phase of cooling from the mid-Miocene onwards and subsequent habitat restructuring has led to the diversification of Antarctic terrestrial taxa, we integrate three tiers of molecular data to reveal a comprehensive evolutionary history for the Ectemnorhinini weevils. This additionally allows us to resolve the geographic, taxonomic, and temporal origins of the Ectemnorhinini and the role of dispersal and colonization in the development of the region’s biogeography. We first resolve the controversial origins of these weevils (19, 30) with a phylogenomic approach using anchored hybrid enrichment (AHE) for up to 515 genes across 12 representative species of Ectemnorhinini and a worldwide sample of 87 species of putative relatives and known outgroups, mostly from the beetle subfamily Entiminae (18, 30, 31). We then build on these outcomes by exploring the timing and patterns of taxonomic diversification, including divergence times and proposed dispersal events, using a multilocus phylogenetic dataset (three mitochondrial and two nuclear genes) for an extensive sample of Ectemnorhinini from each archipelago on which they are known to occur. Finally, we reveal contemporary limits to gene flow and examine the population structure of the littoral-dwelling ectemnorhinine weevil Palirhoeus eatoni using phylogeographic methods applied to a library of 5,859 genome-wide single-nucleotide polymorphisms (SNPs). This unusually widespread species is found on all four archipelagos of the Kerguelen Province known to host Ectemnorhinini: Crozet, Kerguelen, Prince Edward Islands (PEI), and Heard Island and McDonald Islands (HIMI).     

The Value of Claims-Based Nontraditional Risk Factors in Predicting Long-term Mortality After MitraClip Procedure

Background

We sought to identify nontraditional risk factors coded in administrative claims data and evaluate their ability to improve prediction of long-term mortality in patients undergoing percutaneous mitral valve repair.

Acquired factor VII deficiency associated with aplastic anaemia: correction with bone marrow transplantation

We report a patient with severe aplastic anaemia found to have a prolonged prothrombin time due to acquired factor VII deficiency. No evidence for a factor VII inhibitor or inactivator was demonstrable. Laboratory studies identified deficiency both of factor VII activity and factor VII antigen. The factor VII deficiency persisted from clinical presentation until approximately 50 d after allogeneic marrow transplantation when restoration of factor VII activity and antigen was noted. The patient's serum could be depleted of factor VII activity by in vitro incubation with Protein A bound to Sepharose, suggesting the presence of an IgG or IgG containing complex able to bind factor VII, but not neutralize its procoagulant activity. A dual specificity solid phase immunoassay identified a factor VII binding immunoglobulin which was detectable throughout the course of factor VII deficiency. The concordant appearance of this factor VII reactive immunoglobulin and the factor VII deficiency suggested the pathologic role of this immunoglobulin in the aetiology of the factor VII deficiency. This factor VII binding immunoglobulin may have induced rapid plasma clearance of the factor VII molecule or, alternatively, may have modified factor VII synthesis. The immunosuppressive therapy and subsequent lymphohaematopoietic engraftment following allogeneic marrow transplant was accompanied by complete resolution of the factor VII deficiency.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.