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Experimental studies demonstrate the existence of phenotypic diversity despite constant genotype and environment. Theoretical models based on a single phenotypic character predict that during an adaptation event, phenotypic noise should be positively selected far from the fitness optimum because it increases the fitness of the genotype, and then be selected against when the population reaches the optimum. It is suggested that because of this fitness gain, phenotypic noise should promote adaptive evolution. However, it is unclear how the selective advantage of phenotypic noise is linked to the rate of evolution, and whether any advantage would hold for more realistic, multidimensional phenotypes. Indeed, complex organisms suffer a cost of complexity, where beneficial mutations become rarer as the number of phenotypic characters increases. Using a quantitative genetics approach, we first show that for a one-dimensional phenotype, phenotypic noise promotes adaptive evolution on plateaus of positive fitness, independently from the direct selective advantage on fitness. Second, we show that for multidimensional phenotypes, phenotypic noise evolves to a low-dimensional configuration, with elevated noise in the direction of the fitness optimum. Such a dimensionality reduction of the phenotypic noise promotes adaptive evolution and numerical simulations show that it reduces the cost of complexity.
Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered intravenously, intramuscularlyor orally. We assessed the optimal treatment regimen for PID. OBJECTIVES To assess the effectiveness and safety of antibiotic regimens to treat PID.
In January 2020, we searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2020, located through hand and electronic searching; CENTRAL; MEDLINE; Embase; four other databases; and abstracts in selected publications.
We included RCTs comparing antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to a comparison of drugs in current use that are recommended by the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID.
We used stande in severe PID with clindamycin plus aminoglycoside compared to cephalosporin (RR 1.00, 95% CI 0.95 to 1.06; 10 RCTs, 959 women; I
= 21%; moderate-quality evidence). We are uncertain whether clindamycin plus aminoglycoside reduces adverse effects leading to discontinuation of treatment compared to cephalosporin (RR 0.78, 95% CI 0.18 to 3.42; 10 RCTs, 1172 women; I
= 0%; very low-quality evidence).
We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias,a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared totetracycline (doxycycline).
We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias, a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared to tetracycline (doxycycline).
There has been growing interest in the use of xanthine oxidase (XO) as a therapeutic agent to prevent gout and hyperuricemia. In the present study, XO inhibitory peptides were identified from tuna protein by virtual screening, and molecular docking was used to elicit the interaction mechanism between XO and peptides.
A novel tetrapeptide, EEAK, exhibited high XO inhibitory activity with an IC
of 173.00 ± 0.06 μM. Molecular docking analysis revealed that EEAK bound with the pivotal residues of XO's active sites (i.e., Glu802, Arg880, Glu1261) through two conventional hydrogen bond interactions, two attractive charge interactions, and one salt bridge. EEAK could also bind with the residues Phe649, Leu648, Lys771, Ser876, Phe914, and Thr1010 of XO.
This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia. © 2020 Society of Chemical Industry.
This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia. © 2020 Society of Chemical Industry.
Few studies examine why rural public schools have weaker policies and practices related to school nutrition environments compared to their urban counterparts. It is important to understand this disparity because federal school meal standards aim for children to access health-promoting nutrition environments. In this study, we identify challenges and opportunities for the implementation of school meal standards in rural high schools.
We interviewed 38 rural school professionals from 22 high schools across 7 states. School professionals included food service directors, principals, school nurses, and teachers. Team coding in Atlas.ti Qualitative Data Analysis software v8 and principles of comparative analysis were employed to generate themes related to challenges and opportunities.
Overall, school professionals described improvements with implementation experiences and student acceptance over time. Key challenges included the negative influences of home and community food environments and limited staff size and capacity. Key opportunities involved joining co-ops to enhance purchasing power, leveraging state technical assistance, and forming external partnerships.
This study offers insights from a broad range of rural school professionals' implementation experiences. The findings can inform governments and technical assistance agencies working with rural schools and school districts to facilitate implementation and sustainability of initiatives.
This study offers insights from a broad range of rural school professionals' implementation experiences. The findings can inform governments and technical assistance agencies working with rural schools and school districts to facilitate implementation and sustainability of initiatives.Hybridization has important effects on the evolutionary trajectories of natural populations but estimates of this process in the wild and at the individual-level are lacking. Justyn et al. (2020) attempted to fill this gap using the citizen science database eBird but there are limitations to this approach. Here, we outline and directly test these limitations using literature searches, case studies and a comparison between eBird and Birds of North America (BNA), a database that documents hybridization using the scientific literature. We use a hybrid zone between Lazuli and Indigo buntings to highlight the importance of considering geographic range when estimating rates of hybridization and two literature searches to show the importance of considering cryptic hybrids (those that cannot be identified using phenotypic traits) when quantifying these rates. We also use BNA and a case study of hybrid White-faced and Glossy Ibises to show that citizen scientists are under-reporting hybrids compared with experts. Justyn et al. (2020) highlighted an important gap in the literature, but their results likely represent the lower limit of hybridization between birds and a more nuanced interpretation of their results (e.g., considering extrinsic postzygotic selection) is needed. This article is protected by copyright. All rights reserved.
There is no study regarding intraoperative neural monitoring (IONM) of the external branch of the superior laryngeal nerve (EBSLN) during transoral thyroidectomy. The objective of this study was to evaluate the feasibility and success rate of electrical identification of the EBSLN during transoral robotic or endoscopic thyroidectomy.
Case series study.
We studied a cohort of 76 patients (87 nerves at risk, (NARs) who underwent transoral robotic or endoscopic thyroidectomy and simultaneous intermittent IONM between July 2017 and May 2019. We performed the standard IONM procedure plus routine neural monitoring of the EBSLN. IONM and surgical outcome data were prospectively collected.
Sixty-one patients underwent the robotic procedure, and 15 patients underwent the endoscopic procedure. Thirty-seven external branches of the superior laryngeal nerves at risk (42.5%) were electrically identified using electromyography signals (31 NARs, 35.6%) or cricothyroid muscle twitches (6 NARs, 6.9%). The mean pre-(S1) and post-dissection (S2) amplitudes of the EBSLN were 372 ± 147 and 351 ± 159 μV, respectively. The identification rates were not different between the robotic and endoscopic procedures. In comparing the early 20 NARs (18 patients) and the later 67 NARs (58 patients), the identification rate was higher in the later cases, although the difference was not statistically significant (25.0% vs. find more 47.8%, P = .079).
IONM of the EBSLN is feasible and useful in identifying and preserving the nerve during transoral thyroidectomy, although the identification rate of the nerve is relatively low.
4 Laryngoscope, 2020.
4 Laryngoscope, 2020.ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference.
Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148-spiked plasma, and RBC testing including antigen typing was performed on ALX148-coated RBCs. Soluble CD47 or high-affinity signal regulatory protein α (SIRPα) monomers were used to remove the false-positive reactivity of ALX148-spiked plasma with or without anti-E.
ALX148 caused false-positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two-stage papain testing. However, false-positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50- to 100-fold molar excess of soluble CD47 or 300-fold molar excess of high-affinity SIRPα monomers removed false-positive reactivity in IAT without affecting anti-E detection.
ALX148 generates false-positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high-affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies.
ALX148 generates false-positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high-affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies.
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