Study objective Community-associated methicillin-resistant Staphylococcus aureus is now the leading cause of uncomplicated skin abscesses in the United States, and the role of antibiotics is ...controversial. We evaluate whether trimethoprim-sulfamethoxazole reduces the rate of treatment failures during the 7 days after incision and drainage and whether it reduces new lesion formation within 30 days. Methods In this multicenter, double-blind, randomized, placebo-controlled trial, we randomized adults to oral trimethoprim-sulfamethoxazole or placebo after uncomplicated abscess incision and drainage. Using emergency department rechecks at 2 and 7 days and telephone follow-up, we assessed treatment failure within 7 days, and using clinical follow-up, telephone follow-up, and medical record review, we recorded the development of new lesions within 30 days. Results We randomized 212 patients, and 190 (90%) were available for 7-day follow-up. We observed a statistically similar incidence of treatment failure in patients receiving trimethoprim-sulfamethoxazole (15/88; 17%) versus placebo (27/102; 26%), difference 9%, 95% confidence interval –2% to 21%; P =.12. On 30-day follow-up (successful in 69% of patients), we observed fewer new lesions in the antibiotic (4/46; 9%) versus placebo (14/50; 28%) groups, difference 19%, 95% confidence interval 4% to 34%, P =.02. Conclusion After the incision and drainage of uncomplicated abscesses in adults, treatment with trimethoprim-sulfamethoxazole does not reduce treatment failure but may decrease the formation of subsequent lesions.
In the first wave of the "German Health Interview and Examination Survey for Adults" (DEGS1), up-to-date and representative data regarding allergic diseases of 7988 18- to 79-year-old subjects living ...in Germany were collected using computer-assisted medical interviews. The study identified a lifetime prevalence of 8.6% for asthma, 14.8% for allergic rhinoconjunctivitis, 3.5% each for atopic dermatitis and urticaria, 8.1% for contact eczema, 4.7% for food allergies and 2.8% for insect venom allergies. Overall, nearly one third of adults in Germany have been diagnosed with at least one of the above mentioned allergies during their lifetime by a physician. Currently, nearly 20% suffer from at least one allergic disease. Generally, women reported an allergic disease more frequently than men and younger subjects more frequently than older ones. Additionally, allergies are more common in the former federal states of West Germany than in the former East German federal states. A high socioeconomic status and living in large cities both increase allergy risk. During the last 10 years, asthma prevalence increased about 3%, whereas the prevalence of urticaria and contact eczema declined. The lifetime prevalence of allergic rhinoconjunctivitis, atopic dermatitis and food allergies appeared unchanged. In total, allergy prevalence has declined from 32.7-28.7% over the past decade. An English full-text version of this article is available at SpringerLink as supplemental.
Häufigkeit allergischer Erkrankungen in Deutschland Langen, U.; Schmitz, R.; Steppuhn, H.
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz,
05/2013, Letnik:
56, Številka:
5-6
Journal Article
Recenzirano
Zusammenfassung
In der ersten Welle der „Studie zur Gesundheit Erwachsener in Deutschland“ (DEGS1) wurden aktuelle und bundesweit repräsentative Daten zum allergischen Krankheitsgeschehen von 7988 ...18- bis 79-Jährigen mittels computergestützter, ärztlicher Interviews erhoben. Demnach liegt die Lebenszeitprävalenz (LZP) für Asthma bronchiale bei 8,6%, Heuschnupfen bei 14,8%, Neurodermitis und Urtikaria bei jeweils 3,5%, Kontaktekzeme bei 8,1%, Nahrungsmittelallergien bei 4,7% und Insektengiftallergien bei 2,8%. Insgesamt ist bei einem knappen Drittel der Erwachsenen mindestens eine der genannten Allergien jemals ärztlich diagnostiziert worden. Aktuell leiden fast 20% an mindestens einer Allergie. Frauen sind generell häufiger betroffen als Männer und Jüngere häufiger als Ältere. Außerdem sind Allergien in den alten Bundesländern verbreiteter als in den neuen. Ein hoher sozioökonomischer Status und das Leben in Großstädten erhöhen ebenfalls die Krankheitshäufigkeit. Im 10-Jahres-Trend stieg die Asthmaprävalenz um knapp 3%, die Prävalenzen für Urtikaria und Kontaktekzeme sanken, die LZP für Heuschnupfen, Neurodermitis und Nahrungsmittelallergie blieb unverändert. Dadurch ist die Allergieprävalenz insgesamt von 32,7% auf 28,7% rückläufig.
Genetic mutations disrupting the structure and function of primary cilia cause various inherited retinal diseases in humans. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic ...ciliopathy characterized by retinal degeneration, obesity, postaxial polydactyly, intellectual disability, and genital and renal abnormalities. To gain insight into the mechanisms of retinal degeneration in BBS, we developed a congenital knockout mouse of Bbs8, as well as conditional mouse models in which function of the BBSome (a protein complex that mediates ciliary trafficking) can be temporally inactivated or restored. We demonstrate that BBS mutant mice have defects in retinal outer segment morphogenesis. We further demonstrate that removal of Bbs8 in adult mice affects photoreceptor function and disrupts the structural integrity of the outer segment. Notably, using a mouse model in which a gene trap inhibiting Bbs8 gene expression can be removed by an inducible FLP recombinase, we show that when BBS8 is restored in immature retinas with malformed outer segments, outer segment extension can resume normally and malformed outer segment discs are displaced distally by normal outer segment structures. Over time, the retinas of the rescued mice become morphologically and functionally normal, indicating that there is a window of plasticity when initial retinal outer segment morphogenesis defects can be ameliorated.
The porcine ocular surface is used as a model of the human ocular surface; however, a detailed characterization of the porcine ocular surface has not been documented. This is due, in part, to the ...scarcity of antibodies produced specifically against the porcine ocular surface cell types or structures. We performed a histological and immunohistochemical investigation on frozen and formalin-fixed, paraffin-embedded ocular surface tissue from domestic pigs using a panel of 41 different antibodies related to epithelial progenitor/differentiation phenotypes, extracellular matrix and associated molecules, and various niche cell types. Our observations suggested that the Bowman's layer is not evident in the cornea; the deep invaginations of the limbal epithelium in the limbal zone are analogous to the limbal interpalisade crypts of human limbal tissue; and the presence of goblet cells in the bulbar conjunctiva. Immunohistochemistry analysis revealed that the epithelial progenitor markers cytokeratin (CK)15, CK14, p63α, and P-cadherin were expressed in both the limbal and conjunctival basal epithelium, whereas the basal cells of the limbal and conjunctival epithelium did not stain for CK3, CK12, E-cadherin, and CK13. Antibodies detecting marker proteins related to the extracellular matrix (collagen IV, Tenascin-C), cell-matrix adhesion (β-dystroglycan, integrin α3 and α6), mesenchymal cells (vimentin, CD90, CD44), neurons (neurofilament), immune cells (HLA-ABC; HLA-DR, CD1, CD4, CD14), vasculature (von Willebrand factor), and melanocytes (SRY-homeobox-10, human melanoma black-45, Tyrosinase) on the normal human ocular surface demonstrated similar immunoreactivity on the normal porcine ocular surface. Only a few antibodies (directed against N-cadherin, fibronectin, agrin, laminin α3 and α5, melan-A) appeared unreactive on porcine tissues. Our findings characterize the main immunohistochemical properties of the porcine ocular surface and provide a morphological and immunohistochemical basis useful to research using porcine models. Furthermore, the analyzed porcine ocular structures are similar to those of humans, confirming the potential usefulness of pig eyes to study ocular surface physiology and pathophysiology.
IGF‐motif loops project from the hexameric ring of ClpX and are required for docking with the self‐compartmentalized ClpP peptidase, which consists of heptameric rings stacked back‐to‐back. Here, we ...show that ATP or ATPγS support assembly by changing the conformation of the ClpX ring, bringing the IGF loops closer to each other and allowing efficient multivalent contacts with docking clefts on ClpP. In single‐chain ClpX pseudohexamers, deletion of one or two IGF loops modestly slows association with ClpP but strongly accelerates dissociation of ClpXP complexes. We probe how changes in the sequence and length of the IGF loops affect ClpX–ClpP interactions and show that deletion of one or two IGF loops slows ATP‐dependent proteolysis by ClpXP. We also find that ClpXP degradation is less processive when two IGF loops are deleted.
In the framework of a 3-3-1 model with right-handed neutrinos and three scalar triplets we consider different spontaneous symmetry breaking patterns seeking for a non-linear realization of accidental ...symmetries of the model, which will produce physical Nambu–Goldstone (NG) bosons in the neutral scalar spectrum. We make a detailed study of the safety of the model concerning the NG boson emission in energy-loss processes which could affect the standard evolution of astrophysical objects. We consider the model with a
Z
2
symmetry, conventionally used in the literature, finding that in all of the symmetry breaking patterns the model is excluded. Additionally, looking for solutions for that problem, we introduce soft
Z
2
-breaking terms in the scalar potential in order to remove the extra accidental symmetries and at the same time maintain the model as simple as possible. We find that there is only one soft
Z
2
-breaking term that enables us to get rid of the problematic NG bosons.
Significance Caseinolytic peptidase P (ClpP) normally collaborates with ATPases associated with diverse activities (AAA+) partner proteins, such as ClpX and ClpC, to carry out energy-dependent ...degradation of proteins within cells. The ClpP enzyme from Mycobacterium tuberculosis is required for survival of this human pathogen, is a validated drug target, and is unusual in consisting of discrete ClpP1 and ClpP2 rings. We solved the crystal structure of ClpP1P2 bound to peptides that mimic binding of protein substrates and small molecules that mimic binding of a AAA+ partner and cause unregulated rogue proteolysis. These studies explain why two different ClpP rings are required for peptidase activity and provide a foundation for the rational development of drugs that target ClpP1P2 and kill M. tuberculosis .
Caseinolytic peptidase P (ClpP), a double-ring peptidase with 14 subunits, collaborates with ATPases associated with diverse activities (AAA+) partners to execute ATP-dependent protein degradation. Although many ClpP enzymes self-assemble into catalytically active homo-tetradecamers able to cleave small peptides, the Mycobacterium tuberculosis enzyme consists of discrete ClpP1 and ClpP2 heptamers that require a AAA+ partner and protein–substrate delivery or a peptide agonist to stabilize assembly of the active tetradecamer. Here, we show that cyclic acyldepsipeptides (ADEPs) and agonist peptides synergistically activate ClpP1P2 by mimicking AAA+ partners and substrates, respectively, and determine the structure of the activated complex. Our studies establish the basis of heteromeric ClpP1P2 assembly and function, reveal tight coupling between the conformations of each ring, show that ADEPs bind only to one ring but appear to open the axial pores of both rings, provide a foundation for rational drug development, and suggest strategies for studying the roles of individual ClpP1 and ClpP2 rings in Clp-family proteolysis.
An evolutionary epigenetic clock in plants Yao, N.; Zhang, Z.; Yu, L. ...
Science (American Association for the Advancement of Science),
09/2023, Letnik:
381, Številka:
6665
Journal Article
Recenzirano
Odprti dostop
Molecular clocks are the basis for dating the divergence between lineages over macroevolutionary timescales (~10
5
to 10
8
years). However, classical DNA-based clocks tick too slowly to inform us ...about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes display a clocklike behavior. This “epimutation clock” is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation clocks recapitulate known topologies and branching times of intraspecies phylogenetic trees in the self-fertilizing plant
Arabidopsis thaliana
and the clonal seagrass
Zostera marina
, which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.
Editor’s summary
Molecular clocks provide the basis for many population genetic and evolutionary inferences, but are limited in use for recent generations because of low germline mutation rates. In plants, heritable changes in epigenetic markers, known as epimutations, occur at higher rates than genetic mutations. Yao
et al
. were able to develop a tool that allows for the estimation of phylogenies based on these epimutations (see the Perspective by Satyaki). The authors located regions of the genome that experience neutral, clock-like epimutations in the classic plant model
Arabidopsis thaliana
and were able to recapitulate known phylogenies of very recent time scales. This study will help to provide the tools and theoretical basis for estimating recent phylogenies in many plant species. —Corinne Simonti
A fast-ticking evolutionary epigenetic clock in plants facilitates phylogenetic insights into the recent past.
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