Gene Expression Pattern Analysis of Anterior Hox Genes during Zebrafish (Danio rerio) Embryonic Development Reveals Divergent Expression Patterns from Other Teleosts

The regional identity of organs and organ systems along the anterior-posterior axis during embryonic development is patterned, in part, by Hox genes, which encode transcription factor proteins that activate or repress the expression of downstream target genes. Divergent nested Hox gene expression patterns may have had a role in facilitating morphological divergence of structures, such as the pharyngeal jaw apparatus, among evolutionarily divergent teleost fishes. Recent studies from several evolutionarily divergent teleosts, such as the Japanese Medaka (Oryzias latipes) and the Nile Tilapia (Oreochromis niloticus), have shown the presence of divergent expression patterns of several Hox genes within paralog groups 2–5 between these species. Specifically, these expression patterns were documented in the pharyngeal arches, which give rise to the pharyngeal jaw apparatus. While the expression patterns of several Zebrafish (Danio rerio) Hox genes that are orthologous to those of Medaka and Tilapia have been documented within the developing hindbrain and pharyngeal arches, many still have yet to be documented, especially within the pharyngeal arches during the postmigratory cranial neural crest cell stages. Here, we present the expression patterns of six Zebrafish Hox genes, hoxc3a, d3a, a4a, d4a, b5a, and c5a, within the pharyngeal arches during a postmigratory cranial neural crest cell stage and compare them to their orthologous genes of Medaka and Tilapia at similar stages. We show that while hoxc3a, d3a, and c5a of Zebrafish are absent from the pharyngeal arches, hoxa4a, d4a, and b5a show divergent expression patterns from their orthologs in Medaka and Tilapia. These observed divergences may be, in part, responsible for the divergent pharyngeal jaw apparatus structures exhibited by these fishes

Pharmacokinetics of a Single Feeding of Pelleted Cannabidiol in Horses

Claims about cannabidiol (CBD) supplementation improving health and behavior are extensive, but research is lacking. Some studies have shown decreased anxiety behavior in rats, and increased activity in osteoarthritic dogs supplemented with CBD, but even less research exists on horses. This study monitored pharmacokinetics and short-term safety for 3 CBD dosages. Eighteen Quarter Horse geldings were randomly assigned to 3 treatment groups: 50 mg (TXT1), 100 mg (TXT2), and 250 mg (TXT3). Dosage was derived from manufacturer recommendations and existing literature on other species. Horses were fed a single dose of CBD pellets. Blood was collected pre- and post-treatment at 0.5, 1, 2, 4 and 12 hr. Serum was analyzed for CBD and serum chemistry, and plasma was analyzed for a complete blood chemistry (CBC) evaluation. Statistics were completed on serum chemistry using PROC MIXED procedure of SAS. Serum chemistry and CBC results were within normal parameters; however, treatment differences were observed for BUN (TXT1=15.50, TXT2=16.52, TXT3=18.61; P≤0.03) and creatinine (TXT1=1.41, TXT2=1.22, TXT3=1.49; P≤0.01). In other species, peak CBD concentrations occur approximately 2 hr post treatment. Peak serum concentrations were detected in 1 of 6 TXT2 horses and 5 of 6 TXT3 horses at 2 hr post treatment. This data can be used to support further research to determine correct and safe doses of CBD in horses

Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis

The effect of continuous diffusion of oxygen treatment on cytokines, perfusion, bacterial load, and healing in patients with diabetic foot ulcers

To evaluate continuous diffusion of oxygen therapy (CDO) on cytokines, perfusion, and bacterial load in diabetic foot ulcers we evaluated 23 patients for 3 weeks. Tissues biopsies were obtained at each visit to evaluate cytokines and quantitative bacterial cultures. Perfusion was measured with hyperspectral imaging and transcutaneous oxygen. We used paired T tests to compare continuous variables and independent T tests to compare healers and nonhealers. There was an increase from baseline to week 1 in TGF-β (P =.008), TNF-α (P =.014), VEGF (P =.008), PDGF (P =.087), and IGF-1 (P =.058); baseline to week 2 in TGF-β (P =.010), VEGF (P =.051), and IL-6 (P =.031); and baseline to week 3 with TGF-β (P =.055) and IL-6 (P =.054). There was a significant increase in transcutaneous oxygen after 1 week of treatment on both medial and lateral foot (P =.086 and.025). Fifty-three percent of the patients had at least a 50% wound area reduction (healers). At baseline, there were no differences in cytokines between healers and nonhealers. However, there was an increase in CXCL8 after 1 week of treatment (P =.080) and IL-6 after 3 weeks of treatment in nonhealers (P =.099). There were no differences in quantitative cultures in healers and nonhealers

Lyopreserved amniotic membrane is cellularly and clinically similar to cryopreserved construct for treating foot ulcers

We compared cellular viability between cryopreserved and lyopreserved amniotic membranes and clinical outcomes of the lyopreserved construct in a prospective cohort study of 40 patients with neuropathic foot ulcers. Patients received weekly application of lyopreserved membrane for 12 weeks with standard weekly debridement and offloading. We evaluated the proportion of foot ulcers that closed, time to closure, closure trajectories, and infection during therapy. We used chi-square tests for dichotomous variables and independent t-tests for continuous variables with an alpha of α =.10. Cellular viability was equivalent between cryo- and lyopreserved amniotic tissues. Clinically, 48% of subjects' wounds closed in an average of 40.0 days. Those that did not close were older (63 vs 59 years, P =.011) and larger ulcers at baseline (7.8 vs 1.6 cm2, P =.012). Significantly more patients who achieved closure reached a 50% wound area reduction in 4 weeks compared with non-closed wounds (73.7% vs 47.6%, P =.093). There was no difference in the slope of the wound closure trajectories between closed and non-closed wounds (0.124 and 0.159, P =.85), indicating the rate of closure was similar. The rate of closure was 0.60 mm/day (SD = 0.47) for wounds that closed and 0.50 mm/day (SD = 0.58) for wounds that did not close (P =.89)

Induced ectopic expression of HigB toxin in Mycobacterium tuberculosis results in growth inhibition, reduced abundance of a subset of mRNAs and cleavage of tmRNA.

In Mycobacterium tuberculosis, the genes Rv1954A-Rv1957 form an operon that includes Rv1955 and Rv1956 which encode the HigB toxin and the HigA antitoxin respectively. We are interested in the role and regulation of this operon, since toxin-antitoxin systems have been suggested to play a part in the formation of persister cells in mycobacteria. To investigate the function of the higBA locus, effects of toxin expression on mycobacterial growth and transcript levels were assessed in M. tuberculosis H37Rv wild type and in an operon deletion background. We show that expression of HigB toxin in the absence of HigA antitoxin arrests growth and causes cell death in M. tuberculosis. We demonstrate HigB expression to reduce the abundance of IdeR and Zur regulated mRNAs and to cleave tmRNA in M. tuberculosis, Escherichia coli and Mycobacterium smegmatis. This study provides the first identification of possible target transcripts of HigB in M. tuberculosis

Comparing web-based mindfulness with loving-kindness and compassion training for promoting well-being in pregnancy: Protocol for a three-arm pilot randomized controlled trial

© Amy Louise Finlay-Jones, Jacqueline Ann Davis, Amanda O\u27Donovan, Keerthi Kottampally, Rebecca Anne Ashley, Desiree Silva, Jeneva Lee Ohan, Susan L Prescott, Jenny Downs. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.10.2020. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included. Background: Promoting psychological well-being and preventing distress among pregnant women is an important public health goal. In addition to adversely impacting the mother’s health and well-being, psychological distress in pregnancy increases the risk of poor pregnancy outcomes, compromises infant socioemotional development and bonding, and heightens maternal and child vulnerability in the postpartum period. Mindfulness and compassion-based interventions show potential for prevention and early intervention for perinatal distress. As there is an established need for accessible, scalable, flexible, and low-cost interventions, there is increased interest in the delivery of these programs on the web. This project aims to pilot a three-arm randomized controlled trial (RCT) to determine the feasibility of a full-scale RCT comparing 2 web-based interventions (mindfulness vs loving-kindness and compassion) with a web-based active control condition (progressive muscle relaxation). Objective: The primary objective of this study is to assess the feasibility of an RCT protocol comparing the 3 conditions delivered on the web as a series of instructional materials and brief daily practices over a course of 8 weeks. The second objective is to explore the experiences of women in the different intervention conditions. The third objective is to estimate SD values for the outcome measures to inform the design of an adequately powered trial to determine the comparative efficacy of the different conditions. Methods: Pregnant women (n=75) participating in a longitudinal birth cohort study (the ORIGINS project) will be recruited to this study from 18 weeks of gestational age. We will assess the acceptability and feasibility of recruitment and retention strategies and the participants’ engagement and adherence to the interventions. We will also assess the experiences of women in each of the 3 intervention conditions by measuring weekly changes in their well-being and engagement with the program and by conducting a qualitative analysis of postprogram interviews. Results: This project was funded in September 2019 and received ethics approval on July 8, 2020. Enrollment to the study will commence in September 2020. Feasibility of a full-scale RCT will be assessed using ADePT (a process for decision making after pilot and feasibility trials) criteria. Conclusions: If the study is shown to be feasible, results will be used to inform future full-scale RCTs. Evidence for flexible, scalable, and low-cost interventions could inform population health strategies to promote well-being and reduce psychological distress among pregnant women

Biogeochemical and historical drivers of microbial community composition and structure in sediments from Mercer Subglacial Lake, West Antarctica

Ice streams that flow into Ross Ice Shelf are underlain by water-saturated sediments, a dynamic hydrological system, and subglacial lakes that intermittently discharge water downstream across grounding zones of West Antarctic Ice Sheet (WAIS). A 2.06 m composite sediment profile was recently recovered from Mercer Subglacial Lake, a 15 m deep water cavity beneath a 1087 m thick portion of the Mercer Ice Stream. We examined microbial abundances, used 16S rRNA gene amplicon sequencing to assess community structures, and characterized extracellular polymeric substances (EPS) associated with distinct lithologic units in the sediments. Bacterial and archaeal communities in the surficial sediments are more abundant and diverse, with significantly different compositions from those found deeper in the sediment column. The most abundant taxa are related to chemolithoautotrophs capable of oxidizing reduced nitrogen, sulfur, and iron compounds with oxygen, nitrate, or iron. Concentrations of dissolved methane and total organic carbon together with water content in the sediments are the strongest predictors of taxon and community composition. δ¹³C values for EPS (−25 to −30‰) are consistent with the primary source of carbon for biosynthesis originating from legacy marine organic matter. Comparison of communities to those in lake sediments under an adjacent ice stream (Whillans Subglacial Lake) and near its grounding zone provide seminal evidence for a subglacial metacommunity that is biogeochemically and evolutionarily linked through ice sheet dynamics and the transport of microbes, water, and sediments beneath WAIS

The Optical Orbital Light Curve of the Low-mass X-ray Binary V1408 Aquilae (= 4U 1957+115)

V1408 Aql (= 4U 1957+115) is a low-mass X-ray binary with an orbital period near 9.3 hr, whose compact star is a black hole candidate. The system shows a large-amplitude orbital photometric modulation at optical wavelengths. We have obtained new optical photometry of V1408 Aql from which we derive the orbital light curve and an improved orbital ephemeris. We show that the orbital light curve can be reproduced by a model in which the accretion disk around the compact star is thin, axisymmetric, and uneclipsed. The secondary star is heated by X-rays from the compact star and the accretion disk. The orbital modulation is produced entirely by the changing aspect of the irradiated secondary star with orbital phase. Because the system does not eclipse, the fits of the model light curves are insensitive to the orbital parameters, allowing a wide range of orbital inclinations and mass ratios.Comment: 26 pages, 9 figures (3 in color), To appear as ApJ, 730, 43, 201

Changing the antibiotic prescribing of general practice registrars: The ChAP study protocol for a prospective controlled study of a multimodal educational intervention

Background: Australian General Practitioners (GPs) are generous prescribers of antibiotics, prompting concerns including increasing antimicrobial resistance in the community. Recent data show that GPs in vocational training have prescribing patterns comparable with the high prescribing rate of their established GP supervisors. Evidence-based guidelines consistently advise that antibiotics are not indicated for uncomplicated upper respiratory tract infections (URTI) and are rarely indicated for acute bronchitis. A number of interventions have been trialled to promote rational antibiotic prescribing by established GPs (with variable effectiveness), but the impact of such interventions in a training setting is unclear. We hypothesise that intervening while early-career GPs are still developing their practice patterns and prescribing habits will result in better adherence to evidence-based guidelines as manifested by lower antibiotic prescribing rates for URTIs and acute bronchitis. Methods/design: The intervention consists of two online modules, a face-to-face workshop for GP trainees, a face-to-face workshop for their supervisors and encouragement for the trainee-supervisor dyad to include a case-based discussion of evidence-based antibiotic prescribing in their weekly one-on-one teaching meetings. We will use a non-randomised, non-equivalent control group design to assess the impact on antibiotic prescribing for acute upper respiratory infections and acute bronchitis by GP trainees in vocational training. Discussion: Early-career GPs who are still developing their clinical practice and prescribing habits are an underutilized target-group for interventions to curb the growth of antimicrobial resistance in the community. Interventions that are embedded into existing training programs or are linked to continuing professional development have potential to increase the impact of existing interventions at limited additional cost. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12614001209684 (registered 17/11/2014)