Hemiarthroplasty and femoral neck fractures

Nye fremskritt i norsk forskning om protesekirurgi ved lårhalsbrudd Overlege og forsker Paul Wender Figved og medarbeidere viser i en ny doktoravhandling gode resultater ved bruk av to forskjellige typer hofteprotese ved behandling av lårhalsbrudd. Forskere fra den samme gruppen har tidligere fått internasjonal anerkjennelse for å vise at de fleste lårhalsbrudd bør behandles med protese og ikke med skruer. Hvilken type hofteprotese som egner seg best til behandling av lårhalsbrudd er gjenstand for videre forskning. Gjennomsnittsalderen for pasienter med lårhalsbrudd i Norge er rundt 82 år og ca 80% er kvinner. Rundt 10.000 pasienter med brudd i hoften opereres ved norske sykehus hvert år, og rundt halvparten av disse er rene lårhalsbrudd. Diagnosen er forbundet med høy komplikasjonsrate og dødelighet. Bruk av sement ved innsetting av protese er forbundet med sjeldne men svært alvorlige komplikasjoner. Avhandlingen Hemiarthroplasty and femoral neck fractures består av fire vitenskaplige artikler. En klinisk studie med 220 pasienter som ble behandlet med enten en protese festet med sement eller en protese festet uten sement, viste like gode resultater med hensyn til smerter etter operasjonen, grad av fornøydhet og komplikasjoner. Tidligere forskning har vist at det finnes en rekke usementerte proteser som fungerer dårlig ved behandling av lårhalsbrudd, men protesen som ble brukt i denne studien synes å være bedre og er nå i økende bruk i Norge. Pasientene som fikk protese uten sement hadde kortere operasjonstid og mindre blodtap, men dette ga ikke utslag på resultatet av behandlingen. En klinisk studie med en nyutviklet målemetode viste at slitasjen en protese påfører brusken i hofteskålen er så liten at den ikke lar seg måle det første året etter operasjonen. To studier viste at behandlingen av komplikasjoner etter operasjon med protese er vanskelig, at utfallet etter ytterligere kirurgi er særdeles usikkert og forbundet med en rekke ytterligere komplikasjoner

Retrosynthetic reaction prediction using neural sequence-to-sequence models

We describe a fully data driven model that learns to perform a retrosynthetic reaction prediction task, which is treated as a sequence-to-sequence mapping problem. The end-to-end trained model has an encoder-decoder architecture that consists of two recurrent neural networks, which has previously shown great success in solving other sequence-to-sequence prediction tasks such as machine translation. The model is trained on 50,000 experimental reaction examples from the United States patent literature, which span 10 broad reaction types that are commonly used by medicinal chemists. We find that our model performs comparably with a rule-based expert system baseline model, and also overcomes certain limitations associated with rule-based expert systems and with any machine learning approach that contains a rule-based expert system component. Our model provides an important first step towards solving the challenging problem of computational retrosynthetic analysis

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Confirming the existence of π-allyl-palladium intermediates during the reaction of meta photocycloadducts with palladium(ii) compounds

The transient existence of π-allyl-palladium intermediates formed by the reaction of Pd(OAc)2 and anisole-derived meta photocycloadducts has been demonstrated using NMR techniques. The intermediates tended to be short-lived and underwent rapid reductive elimination of palladium metal to form allylic acetates, however this degradation process could be delayed by changing the reaction solvent from acetonitrile to chloroform

Comparison of three video laryngoscopy devices to direct laryngoscopy for intubating obese patients: a randomized controlled trial

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Are language production problems apparent in adults who no longer meet diagnostic criteria for attention-deficit/hyperactivity disorder?

In this study, we examined sentence production in a sample of adults (N = 21) who had had attention-deficit/hyperactivity disorder (ADHD) as children, but as adults no longer met DSM-IV diagnostic criteria (APA, 2000). This “remitted” group was assessed on a sentence production task. On each trial, participants saw two objects and a verb. Their task was to construct a sentence using the objects as arguments of the verb. Results showed more ungrammatical and disfluent utterances with one particular type of verb (i.e., participle). In a second set of analyses, we compared the remitted group to both control participants and a “persistent” group, who had ADHD as children and as adults. Results showed that remitters were more likely to produce ungrammatical utterances and to make repair disfluencies compared to controls, and they patterned more similarly to ADHD participants. Conclusions focus on language output in remitted ADHD, and the role of executive functions in language production