Explore the vast range of titles available.

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α 2-δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

The efficacy of drugs for neuropathic pain has been established in randomized controlled trials that have excluded patients with comorbid conditions and those taking complex medications. However, patients with neuropathic pain frequently present with complex histories, making direct application of this evidence problematic. Treatment of neuropathic pain needs to be individualized according to the cause of the pain, concomitant diseases, medications, and other individual factors. Tricyclic antidepressants (TCAs), gabapentinoids, selective noradrenergic reuptake inhibitors, and topical lidocaine are the first-line choices; if needed, combination therapy may be used. When a new drug is added, screening for potential drug interactions is recommended. The TCAs have anticholinergic adverse effects and may cause orthostatic hypotension. They should be avoided or used cautiously in patients with cardiac conduction disturbances or arrhythmias. Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol. A combination of several serotoninergic drugs may lead to serotonin syndrome. Risk of gastrointestinal tract bleeding is increased in patients taking selective serotonin reuptake inhibitors or venlafaxine, especially when combined with nonsteroidal anti-inflammatory drugs. Dose adjustment may be needed in patients with renal or hepatic impairment. Depending on the drug, the dose is reduced or the dosage interval lengthened. Slow titration and careful follow-up are needed. No drug is absolutely safe during pregnancy and lactation. Particular care must be exercised during the first trimester when drug dose should be as low as possible. Individual weighing of benefits and risks should guide therapeutic decisions.

Ubiquitous white earbuds and declining album sales were visual and economic indicators of the trend that will likely be most remembered from 2005 - the year in which the music world tipped toward digital downloading. True, millions of albums are still being sold. But the number of songs downloaded, both legally and illegally, continues to spiral upward, and millions of people who hadn't been part of the brave new musical world got themselves iPods and similar players and joined the revolution. The U2/Kanye West concert at Omaha's Qwest Center earlier this month was one of the best shows ever in Nebraska. Period. End of story. U2 is one of the world's best live acts, and their passionate Qwest Center performance was the best I've seen from them. And West, who played with a string section, is as captivating and charismatic live as he is on record. 1. [Jack White] and Meg White of the White Stripes perform during the Annual Grammy Awards in 2004 in Los Angeles. KEVORK DJANSEZIAN/Asscoiated Press file photo 2. Mike Overfield (from left), Austin Skiles, Britt Hayes, Carrie Butler, Luther Mardock, Johnny Idt and Eli Mardock are Eagle*Seagull, one odf the year's most accomplished local groups. COURTESY PHOTO

Cationic antimicrobial peptides and their therapeutic potential have garnered growing interest because of the proliferation of bacterial resistance. However, the discovery of new antimicrobial peptides from animals has proven challenging due to the limitations associated with conventional biochemical purification and difficulties in predicting active peptides from genomic sequences, if known. As an example, no antimicrobial peptides have been identified from the American alligator, Alligator mississippiensis, although their serum is antimicrobial. We have developed a novel approach for the discovery of new antimicrobial peptides from these animals, one that capitalizes on their fundamental and conserved physico-chemical properties. This sample-agnostic process employs custom-made functionalized hydrogel microparticles to harvest cationic peptides from biological samples, followed by de novo sequencing of captured peptides, eliminating the need to isolate individual peptides. After evaluation of the peptide sequences using a combination of rational and web-based bioinformatic analyses, forty-five potential antimicrobial peptides were identified, and eight of these peptides were selected to be chemically synthesized and evaluated. The successful identification of multiple novel peptides, exhibiting antibacterial properties, from Alligator mississippiensis plasma demonstrates the potential of this innovative discovery process in identifying potential new host defense peptides.

[Joel Gehringer]'s comments: When I initially checked out Tam O'Shanter's burger, it didn't take long to rate it. One or two bites in, it blew my other top restaurant burgers out of the water. Tam's is a fancy, sharp lookin' burger, and with its freshly grilled taste and mouth- watering juices I could've sworn I was eating steak instead of ground beef. [Jeff Korbelik]'s comments: Not surprisingly, Fred and Ruby's burger at Parkway Lanes topped our list. I wrote in a column last fall that Parkway's burger was my favorite, and nothing has changed. Fred uses the recipe from King's, the once-and-mighty local burger chain. He hand pats each burger and applies just the right amount of spices. [Kent Wolgamott]'s comments: I've always been a fan of [Runza]'s burgers and I like the use of ranch dressing on the Legend. Culver's burgers are also excellent, for fast food. And I'd throw in Don & Millie's Don burger as an honorable mention, especially if you're really hungry.

Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.

Phylogenetic relationships among the four major lineages of land plants (liverworts, mosses, hornworts, and vascular plants) remain vigorously contested; their resolution is essential to our understanding of the origin and early evolution of land plants. We analyzed three different complementary data sets: a multigene supermatrix, a genomic structural character matrix, and a chloroplast genome sequence matrix, using maximum likelihood, maximum parsimony, and compatibility methods. Analyses of all three data sets strongly supported liverworts as the sister to all other land plants, and analyses of the multigene and chloroplast genome matrices provided moderate to strong support for hornworts as the sister to vascular plants. These results highlight the important roles of liverworts and hornworts in two major events of plant evolution: the water-to-land transition and the change from a haploid gametophyte generation-dominant life cycle in bryophytes to a diploid sporophyte generation-dominant life cycle in vascular plants. This study also demonstrates the importance of using a multifaceted approach to resolve difficult nodes in the tree of life. In particular, it is shown here that densely sampled taxon trees built with multiple genes provide an indispensable test of taxon-sparse trees inferred from genome sequences.

Interactive graphical genome browsers are essential tools in genomics, but they do not contain all the recent genome assemblies. We create Genome Archive (GenArk) collection of UCSC Genome Browsers from NCBI assemblies. Built on our established track hub system, this enables fast visualization of annotations. Assemblies come with gene models, repeat masks, BLAT, and in silico PCR. Users can add annotations via track hubs and custom tracks. We can bulk-import third-party resources, demonstrated with TOGA and Ensembl gene models for hundreds of assemblies. Three thousand two hundred sixty-nine GenArk assemblies are listed at https://hgdownload.soe.ucsc.edu/hubs/ and can be searched for on the Genome Browser gateway page.