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In 2008 the National Institutes of Health established the Research, Condition and Disease Categorization Database (RCDC) that reports the amount spent by NIH institutes for each disease. Its goal is to allow the public “to know how the NIH spends their tax dollars,” but it has been little used. The RCDC for 2018 was used to assess 428 schizophrenia-related research projects funded by the National Institute of Mental Health. Three senior psychiatrists independently rated each on its likelihood (“likely”, “possible”, “very unlikely”) of improving the symptoms and/or quality of life for individuals with schizophrenia within 20 years. At least one reviewer rated 386 (90%), and all three reviewers rated 302 (71%), of the research projects as very unlikely to provide clinical improvement within 20 years. Reviewer agreement for the “very unlikely” category was good; for the “possible” category was intermediate; and for the “likely” category was poor. At least one reviewer rated 30 (7%) of the research projects as likely to provide clinical improvement within 20 years. The cost of the 30 projects was 5.5% of the total NIMH schizophrenia-related portfolio or 0.6% of the total NIMH budget. Study results confirm previous 2016 criticisms that the NIMH schizophrenia-related research portfolio disproportionately underfunds clinical research that might help people currently affected. Although the results are preliminary, since the RCDC database has not previously been used in this manner and because of the subjective nature of the assessment, the database would appear to be a useful tool for disease advocates who wish to ascertain how NIH spends its public funds.

To determine whether perineural dexamethasone prolongs peripheral nerve blockade (PNB) when measured objectively; and to determine if a 1 mg and 4 mg dose provide equivalent PNB prolongation compared to PNB without dexamethasone. Multiple studies have reported that perineural dexamethasone added to local anesthetics (LA) can prolong PNB. However, these studies have relied on subjective end-points to quantify PNB duration. The optimal dose remains unknown. We hypothesized that 1 mg of perineural dexamethasone would be equivalent in prolonging an adductor canal block (ACB) when compared to 4 mg of dexamethasone, and that both doses would be superior to an ACB performed without dexamethasone. This was a prospective, randomized, double-blind, placebo-controlled equivalency trial involving 85 patients undergoing a unicompartmental knee arthroplasty. All patients received an ACB with 20 ml of 0.25% bupivacaine with 1:400,000 epinephrine. Twelve patients had 0 mg of dexamethasone (placebo) added to the LA mixture; 36 patients had 1 mg of dexamethasone in the LA; and 37 patients had 4 mg of dexamethasone in the LA. The primary outcome was block duration determined by serial neurologic pinprick examinations. Secondary outcomes included time to first analgesic, serial pain scores, and cumulative opioid consumption. The 1 mg (31.8 ± 10.5 h) and 4 mg (37.9 ± 10 h) groups were not equivalent, TOST [Mean difference (95% CI); 6.1 (−10.5, −2.3)]. Also, the 4 mg group was superior to the 1 mg group (p-value = 0.035), and the placebo group (29.7 ± 6.8 h, p-value = 0.011). There were no differences in opioid consumption or time to analgesic request; however, some pain scores were significantly lower in the dexamethasone groups when compared to placebo. Dexamethasone 4 mg, but not 1 mg, prolonged the duration of an ACB when measured by serial neurologic pinprick exams. NCT02462148 •Serial pin-prick examination revealed that 4 mg of dexamethasone prolongs adductor canal peripheral nerve blockade (PNB).•Unlike 4 mg, 1 mg of perineural dexamethasone does not prolong PNB.•Pain scores were lower in the dexamethasone groups, particularly with movement.•There were no differences in time to first analgesic request or opioid consumption amongst the three groups.

A randomized trial evaluating spinal as compared with general anesthesia for hip-fracture surgery in adults 50 years of age or older did not show superiority of spinal anesthesia with respect to a composite of death or an inability to walk unassisted at 60 days. Postoperative delirium occurred in similar percentages of patients in the two groups.

BackgroundOpen inguinal herniorrhaphy (OIH) is a commonly performed surgical procedure with expected postoperative pain. Historically, an option for regional analgesia has been an ilioinguinal and iliohypogastric nerve block (IINB). More recently, the transmuscular quadratus lumborum block (QLB) has been used as an analgesic technique for a variety of abdominal and truncal surgical procedures. Given our own institutional experiences with the performance of QLB combined with the body of literature supporting the proximal blockade of the ilioinguinal and iliohypogastric nerves via this approach, we compared the analgesia provided by an IINB to a QLB. We hypothesized that the two blocks would provide equivalent analgesia, as defined by a difference of less than±2 points on the pain scale (0–10 numeric rating scale (NRS)), for patients undergoing OIH.MethodsSixty patients scheduled for elective outpatient OIH under general anesthesia were randomized to preoperatively receive either an IINB or a transmuscular QLB with 0.25% bupivacaine/epinephrine/clonidine for postoperative analgesia. The primary endpoint was movement NRS pain scores at 8 hours. Secondary outcomes included resting NRS pain scores at 8 and 24 hours, movement NRS pain scores at 24 hours, incidence of opioid related side effects (nausea, vomiting, pruritus), time-to-first oral opioid analgesic, and total opioid consumption at 24 hours.ResultsFifty-nine patients were analyzed per an intention-to-treat approach (one patient was excluded because the surgical procedure was canceled). Movement pain scores at 8 hours were equivalent (IINB 5.10±3.02 vs QLB 5.03±3.01 (mean NRS±SD); two one-sided test mean difference (90% CI), 0.07 (−1.24 to 1.38), p ≤0.01). There were no differences between groups for any of the secondary endpoints.ConclusionAn IINB and a transmuscular QLB are equivalent with regards to their ability to provide postoperative analgesia after OIH.

SAR11: basking in the light Proteorhodopsin genes were discovered, as DNA fragments in sea water, long before anybody knew what organisms they came from. They encode light-dependent proton pumps that are thought to have a central role in ocean ecology by supplying the energy for microbial metabolism, and now the intact proteorhodopsin system has been tracked down. It is found in SAR11, one of the most abundant organisms on the planet. SAR11, recently renamed Pelagibacter ubique , was synonymous with uncultured microbial diversity until it was first cultured in 2002. These organisms have proteorhodopsin proton pumps and have the odd (for a light-gatherer) ability to grow equally as well in the dark as in the light. SAR11 is out there in the oceans competing with the likes of cyanobacteria for a niche amongst the bacterioplankton. Now it seems that the cyanobacteria may have outside assistance. Viruses (or phages) that infect the ubiquitous cyanobacteria Prochlorococcus do more than just use their DNA to force the host to make more phage. The viral genome contains photosynthesis genes, possibly captured from cyanobacterial hosts long ago. These encode proteins that combine with host photosynthetic machinery to ensure that the host provides the phage with the energy necessary to produce phage progeny. Cyanobacteria, and the viruses (phages) that infect them, are significant contributors to the oceanic ‘gene pool’ 1 , 2 . This pool is dynamic, and the transfer of genetic material between hosts and their phages 3 , 4 , 5 , 6 probably influences the genetic and functional diversity of both. For example, photosynthesis genes of cyanobacterial origin have been found in phages that infect Prochlorococcus 5 , 7 and Synechococcus 8 , 9 , the numerically dominant phototrophs in ocean ecosystems. These genes include psbA , which encodes the photosystem II core reaction centre protein D1, and high-light-inducible ( hli ) genes. Here we show that phage psbA and hli genes are expressed during infection of Prochlorococcus and are co-transcribed with essential phage capsid genes, and that the amount of phage D1 protein increases steadily over the infective period. We also show that the expression of host photosynthesis genes declines over the course of infection and that replication of the phage genome is a function of photosynthesis. We thus propose that the phage genes are functional in photosynthesis and that they may be increasing phage fitness by supplementing the host production of these proteins.

A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (ChIP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth.

Background Loss of resistance (LOR) for epidural catheter placement has been utilized for almost a century. LOR is a subjective endpoint associated with a high failure rate. Nerve stimulation (NS) has been described as an objective method for confirming placement of an epidural catheter. We hypothesized that the addition of NS to LOR would improve the success of epidural catheter placement. Methods One-hundred patients were randomized to thoracic epidural analgesia (TEA) utilizing LOR-alone or loss of resistance plus nerve stimulation (LOR + NS). The primary endpoint was rate of success, defined as loss of sensation following test dose. Secondary endpoints included performance time. An intention-to-treat analysis was planned, but a per-protocol analysis was performed to investigate the success rate when stimulation was achieved. Results In the intention-to-treat analysis there was no difference in success rates (90% vs 82% [LOR + NS vs LOR-alone]; P  = 0.39). The procedural time increased in the LOR + NS group (33.9 ± 12.8 vs 24.0 ± 8.0 min; P  < 0.001). The per-protocol analysis found a statistically higher success rate for the LOR + NS group compared to the LOR-alone group (98% vs. 82%; P  = 0.017) when only patients in whom stimulation was achieved were included. Conclusions Addition of NS technique did not statistically improve the success rate for epidural placement when analyzed in an intention-to-treat format and was associated with a longer procedural time. In a per-protocol analysis a statistically higher success rate for patients in whom stimulation was obtained highlights the potential benefit of adding NS to LOR. Trial registration ClinicalTrials.gov identifier NCT03087604 on 3/22/2017; Institutional Review Board Wake Forest School of Medicine IRB00039522, Food and Drug Administration Investigational Device Exemption: G160273.