bluuebunny/crossref_metadata_2025 huggingface dataset:
Dictyostelium discoideum Nuclear Plasmid Ddp5 Is a Chimera Related to the Ddp1 and Ddp2 Plasmid Families
Authors: Rieben W Kurt , Gonzales Chad M , Gonzales Shane T , Pilkington Katharine J , Kiyosawa Hidenori , Hughes Joanne E , Welker Dennis L
Published: February 2021

The 14,955-bp Dictyostelium discoideum nuclear plasmid Ddp5 contains six transcribed open reading frames. One of these is related to the rep gene of the Ddp2 plasmid, and the other five are related to genes present on the Ddp1 plasmid. The absence of a homolog of the Ddp1 G1 gene, coupled with the presence of the Ddp2 rep gene homolog and of a 1.6-kb inverted repeat analogous to the inverted repeats on members of the Ddp2 plasmid family, suggests that Ddp5 uses Ddp2-like replication and copy number control mechanisms and that it should be assigned to the Ddp2 plasmid family. Ddp5 carries genes homologous to the D1/D3 and D2 genes of the Ddp1 plasmid as well as the Ddp1 G2/G3/D4, G5/D6, and G6/G4/D5 genes. The products of the Ddp5 G2-like, G5-like, and G6-like genes are likely to be transcription factors regulating the expression of themselves and of the other Ddp5 genes. The D1-like and D2-like genes may confer a selective advantage to plasmid-bearing cells, because they can be deleted from plasmid-based shuttle vectors with no apparent effect on vector maintenance. Updated sequence information for the Ddp1 G5/D6, D1/D3, and D2 genes as well as the Dmp1 and Dmp2 G5-like genes is presented. The locations of introns in the G5-like and D1-like genes of Ddp5 and in the homologous genes of the Ddp1, Dmp1, and Dmp2 plasmids were identified. These introns all have GU at the 5′ intron border and AG at the 3′ intron border, are short (59 to 71 nucleotides), and are AT-rich. A conserved HHCC domain was identified in the G5 proteins; this is a putative zinc binding domain and may be involved in protein-DNA interaction.
Conditions for Positive and Negative Correlations Between Fitness and Heterozygosity in Equilibrium Populations
Authors: Deng Hong-Wen , Fu Yun-Xin
Published: February 2021

The past decades have witnessed extensive efforts to correlate fitness traits with genomic heterozygosity. While positive correlations are revealed in most of the organisms studied, results of no/negative correlations are not uncommon. There has been little effort to reveal the genetic causes of these negative correlations. The positive correlations are regarded either as evidence for functional overdominance in large, randomly mating populations at equilibrium, or the results of populations at disequilibrium under dominance. More often, the positive correlations are viewed as a phenomenon of heterosis, so that it cannot possibly occur under within-locus additive allelic effects. Here we give exact genetic conditions that give rise to positive and negative correlations in populations at Hardy-Weinberg and linkage equilibria, thus offering a genetic explanation for the observed negative correlations. Our results demonstrate that the above interpretations concerning the positive correlations are not complete or even necessary. Such a positive correlation can result under dominance and potentially under additivity, even in populations where associated overdominance due to linked alleles at different loci is not significant. Additionally, negative correlations and heterosis can co-occur in a single population. Although our emphasis is on equilibrium populations and for biallelic genetic systems, the basic conclusions are generalized to non-equilibrium populations and for multi-allelic situations.
The Accuracy of Marker-Assisted Selection for Quantitative Traits Within Populations in Linkage Equilibrium
Authors: Ollivier Louis
Published: February 2021

Using the concept of conditional coancestry, given observed markers, an explicit expression of the accuracy of marker-based selection is derived in situations of linkage equilibrium between markers and quantitative trait loci (QTL), for the general case of full-sib families nested within half-sib families. Such a selection scheme is rather inaccurate for moderate values of family sizes and QTL variance, and the accuracies predicted for linkage disequilibrium can never be reached. The result is used to predict the accuracy of marker-assisted combined selection (MACS) and is shown to agree with previous MACS results obtained by simulation of a best linear unbiased prediction animal model. Low gains in accuracy are generally to be expected compared to standard combined selection. The maximum gain, assuming infinite family size and all QTLs marked, is about 50%.
The Yeast HSM3 Gene Acts in One of the Mismatch Repair Pathways
Authors: Fedorova Irina V , Gracheva Ludmila M , Kovaltzova Svetlana V , Evstuhina Tatyana A , Alekseev Sergey Yu , Korolev Vladimir G
Published: February 2021

Mutants with enhanced spontaneous mutability (hsm) to canavanine resistance were induced by N-methyl-N-nitrosourea in Saccharomyces cerevisiae. One bearing the hsm3-1 mutation was used for this study. This mutation does not increase sensitivity to the lethal action of different mutagens. The hsm3-1 mutation produces a mutator phenotype, enhancing the rates of spontaneous mutation to canavanine resistance and reversions of lys1-1 and his1-7. This mutation increases the rate of intragenic mitotic recombination at the ADE2 gene. The ability of the hsm3 mutant to correct DNA heteroduplex is reduced in comparison with the wild-type strain. All these phenotypes are similar to ones caused by pms1, mlhl, and msh2 mutations. In contrast to these mutations, hsm3-1 increases the frequency of ade mutations induced by 6-HAP and UV light. Epistasis analysis of double mutants shows that the PMS1 and HSM3 genes control different mismatch repair systems. The HSM3 gene maps to the right arm of chromosome II, 25 cM distal to the HIS7 gene. Strains that bear a deleted open reading frame YBR272c have the genetic properties of the hsm3 mutant. The HSM3 product shows weak similarity to predicted products of the yeast MSH genes (homologs of the Escherichia coli mutS gene). The HSM3 gene may be a member of the yeast MutS homolog family, but its function in DNA metabolism differs from the functions of other yeast MutS homologs.
Adaptive Mutation: Has the Unicorn Landed?
Authors: Foster Patricia L
Published: February 2021

Reversion of an episomal Lac− allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not “adaptive” in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.
DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding
Authors: Goodman Myron F , Fygenson D Kuchnir
Published: February 2021

This review summarizes mutagenesis studies, emphasizing the use of bacteriophage T4 mutator and antimutator strains. Early genetic studies on T4 identified mutator and antimutator variants of DNA polymerase that, in turn, stimulated the development of model systems for the study of DNA polymerase fidelity in vitro. Later enzymatic studies using purified T4 mutator and antimutator polymerases were essential in elucidating mechanisms of base selection and exonuclease proofreading. In both cases, the base analogue 2-aminopurine (2AP) proved tremendously useful—first as a mutagen in vivo and then as a probe of DNA polymerase fidelity in vitro. Investigations into mechanisms of DNA polymerase fidelity inspired theoretical models that, in turn, called for kinetic and thermodynamic analyses. Thus, the field of DNA synthesis fidelity has grown from many directions: genetics, enzymology, kinetics, physical biochemistry, and thermodynamics, and today the interplay continues. The relative contributions of hydrogen bonding and base stacking to the accuracy of DNA synthesis are beginning to be deciphered. For the future, the main challenges lie in understanding the origins of mutational hot and cold spots.
Regulation of Phosphate Assimilation in Rhizobium (Sinorhizobium) meliloti
Authors: Bardin Sylvie D , Finan Turlough M
Published: February 2021

We report the isolation of phoB and phoU mutants of the bacterium Rhizobium (Sinorhizobium) meliloti. These mutants form N2-fixing nodules on the roots of alfalfa plants. R. meliloti mutants defective in the phoCDET (ndvF) encoded phosphate transport system grow slowly in media containing 2 mm Pi, and form nodules which fail to fix nitrogen (Fix−). We show that the transfer of phoB or phoU insertion mutations into phoC mutant strains restores the ability of these mutants to: (i) form normal N2-fixing root-nodules, and (ii) grow like the wild type in media containing 2 mm Pi. We also show that expression of the alternate orfA pit encoded Pi transport system is negatively regulated by the phoB gene product, whereas phoB is required for phoCDET expression. We suggest that in R. meliloti cells growing under Pi limiting conditions, PhoB protein activates phoCDET transcription and represses orfA pit transcription. Our results suggest that there are major differences between the Escherichia coli and R. meliloti phosphate regulatory systems.
Epistatic Interactions Between smell-impaired Loci in Drosophila melanogaster
Authors: Fedorowicz Grażyna M , Fry James D , Anholt Robert R H , Mackay Trudy F C
Published: February 2021

Odor-guided behavior is a polygenic trait determined by the concerted expression of multiple loci. Previously, P-element mutagenesis was used to identify single P[lArB] insertions, in a common isogenic background, with homozygous effects on olfactory behavior. Here, we have crossed 12 lines with these smell impaired (smi) mutations in a half-diallel design (excluding homozygous parental genotypes and reciprocal crosses) to produce all possible 66 doubly heterozygous hybrids with P[lArB] insertions at two distinct locations. The olfactory behavior of the transheterozygous progeny was measured using an assay that quantified the avoidance response to the repellent odorant benzaldehyde. There was significant variation in general combining abilities of avoidance scores among the smi mutants, indicating variation in heterozygous effects. Further, there was significant variation among specific combining abilities of each cross, indicating dependencies of heterozygous effects on the smi locus genotypes, i.e., epistasis. Significant epistatic interactions were identified for nine transheterozygote genotypes, involving 10 of the 12 smi loci. Eight of these loci form an interacting ensemble of genes that modulate expression of the behavioral phenotype. These observations illustrate the power of quantitative genetic analyses to detect subtle phenotypic effects and point to an extensive network of epistatic interactions among genes in the olfactory subgenome.
Genetic Basis of Response to 50 Generations of Selection on Body Weight in Inbred Mice
Authors: Keightley Peter D
Published: February 2021

A long-established inbred strain of mice was divergently selected for body weight for 50 generations. Selection of new mutations affecting the trait eventually led to a divergence of approximately three phenotypic standard deviations between the high and low lines. Heritability for body weight increased at a rate between 0.23% and 0.57% per generation from new mutations, depending on the genetic model assumed. About two-thirds of the selection response was in the upward direction. The response was episodic, suggesting a substantial contribution from the selection of mutations with large effects on the trait. A maximum likelihood procedure was used to estimate the number of factors contributing to the response using data from line crosses, with models of n equivalent gene effects (i.e., to estimate the Wright-Castle index), or n genes with variable effects. The results of the analysis of data from a cross between the selected high line and an unselected control line indicated that two major factors were involved, with the suggestion of an additional minor factor.
The Isolation and Characterization of nrc-1 and nrc-2, Two Genes Encoding Protein Kinases That Control Growth and Development in Neurospora crassa
Authors: Kothe Gregory O , Free Stephen J
Published: February 2021

Using an insertional mutagenesis approach, a series of Neurospora crassa mutants affected in the ability to control entry into the conidiation developmental program were isolated. One such mutant, GTH16-T4, was found to lack normal vegetative hyphae and to undergo constitutive conidiation. The affected gene has been named nrc-1, for nonrepressible conidiation gene #1. The nrc-1 gene was cloned from the mutant genomic DNA by plasmid rescue, and was found to encode a protein closely related to the protein products of the Saccharomyces cerevisiae STE11 and Schizosaccharomyces pombe byr2 genes. Both of these genes encode MAPKK kinases that are necessary for sexual development in these organisms. We conclude the nrc-1 gene encodes a MAPKK kinase that functions to repress the onset of conidiation in N. crassa. A second mutant, GTH16-T17, was found to lack normal vegetative hyphae and to constitutively enter, but not complete, the conidiation program. The affected locus is referred to as nrc-2 (nonrepressible conidiation gene #2). The nrc-2 gene was cloned and found to encode a serine-threonine protein kinase. The kinase is closely related to the predicted protein products of the S. pombe kad5, and the S. cerevisiae YNRO47w and KIN82 genes, three genes that have been identified in genome sequencing projects. The N. crassa nrc-2 gene is the first member of this group of kinases for which a phenotype has been defined. We conclude a functional nrc-2-encoded serine/threonine kinase is required to repress entry into the conidiation program.
Male Sterility and Meiotic Drive Associated With Sex Chromosome Rearrangements in Drosophila: Role of X-Y Pairing
Authors: McKee Bruce D , Wilhelm Kathy , Merrill Cynthia , Ren Xiao-jia
Published: February 2021

In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh−/Y males, and to restore fertility to Xh−/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.
Evidence for a Genomic Imprinting Sex Determination Mechanism in Nasonia vitripennis (Hymenoptera; Chalcidoidea)
Authors: Dobson Stephen L , Tanouye Mark A
Published: February 2021

Five different models have been proposed for the sex determination mechanism of Chalcidoidea (Hymenoptera). Except for the most recently proposed model (genomic imprinting sex determination; GISD), each of these models has required complicating additions to explain observed phenomena. This report provides the first experimental test of the GISD model while simultaneously examining the four previously proposed models of sex determination. This test utilizes the parasitic wasp Nasonia vitripennis, crossing polyploid females with males harboring the paternal sex ratio chromosome (PSR). The results of this study support the GISD model as the mechanism of sex determination in Chalcidoidea. Specifically, crosses demonstrate that sex determination is independent of embryonic heterozygosity, ploidy, and gametic syngamy but is directly correlated with the embryonic presence of correctly imprinted chromosomes of paternal origin. These crossing experiments also provide information about the poorly characterized mechanisms of PSR, a supernumerary chromosome that induces paternal autosome loss in early embryos. The results demonstrate that the poor transmission of PSR through females is not a result of the ploidy of the host but of an alternative sex-dependent process. Crossing data reveal that PSR consistently induces the loss of the entire paternal complement that it accompanies, regardless of whether this complement is haploid or diploid.
Isolation and Characterization of Arabidopsis Mutants Defective in the Induction of Ethylene Biosynthesis by Cytokinin
Authors: Vogel John P , Schuerman Peter , Woeste Keith , Brandstatter Ingrid , Kieber Joseph J
Published: February 2021

Cytokinins elevate ethylene biosynthesis in etiolated Arabidopsis seedlings via a post-transcriptional modification of one isoform of the key biosynthetic enzyme ACC synthase. In order to begin to dissect the signaling events leading from cytokinin perception to this modification, we have isolated a series of mutants that lack the ethylene-mediated triple response in the presence of cytokinin due to their failure to increase ethylene biosynthesis. Analysis of genetic complementation and mapping revealed that these Cin mutants (cytokinin-insensitive) represent four distinct complementation groups, one of which, cin4, is allelic to the constitutive photomorphogenic mutant fus9/cop10. The Cin mutants have subtle effects on the morphology of adult plants. We further characterized the Cin mutants by analyzing ethylene biosynthesis in response to various other inducers and in adult tissues, as well as by assaying additional cytokinin responses. The cin3 mutant did not disrupt ethylene biosynthesis under any other conditions, nor did it disrupt any other cytokinin responses. Only cin2 disrupted ethylene biosynthesis in multiple circumstances. cin1 and cin2 made less anthocyanin in response to cytokinin. cin1 also displayed reduced shoot initiation in tissue culture in response to cytokinin, suggesting that it affects a cytokinin signaling element.
The Matter of Race: Brotherhood of St. Moses the Black and the Retelling of African American History through Orthodox Christian Forms
Authors: Kravchenko Elena V
Published: February 2021

This article looks at how contemporary African American converts to Orthodox Christianity, specifically the members of the Brotherhood of St. Moses the Black,1 use religion to understand and remember the struggle of Black people against racial discrimination in the United States. As I examine how practitioners interpreted and preserved African American history—the attempts to abolish slavery, the fight to end lynching, and the Civil Rights movement—through Orthodox forms of materiality, I demonstrate that African Americans drew on an established tradition to authorize new ways of practicing Orthodoxy and being Orthodox. I argue that by using icons of the Theotokos to tell stories about her intervention during a lynching, memorializing lives of Black American martyrs in cemetery stones, and engaging with relics of African American saints, these practitioners followed in the footsteps of other Orthodox people—who creatively adopted the ritual life of the Church to their own needs while making an effort to adhere to its traditional dogmatism—and therefore should be considered as a paradigmatic and not an exceptional example of Orthodox Christians.
Comparative analysis of Australian hospital antimicrobial utilization, using the WHO AWaRe classification system and the adapted Australian Priority Antimicrobial List (PAL)
Authors: Hillock Nadine T , Connor Erin , Wilson Courtenay , Kennedy Brendan
Published: February 2021

Background

In 2020 the Australian Priority Antibacterial List (PAL) was developed to support national surveillance of antibacterial usage.

Objectives

To compare the WHO AwaRe classification system with the Australian PAL to analyse antibacterial utilization in Australian acute care hospitals.

Methods

Monthly antibacterial usage rates (defined daily dose per 1000 occupied bed days) were calculated using pharmacy dispensing records together with patient occupancy data for all acute care hospitals contributing to the National Antimicrobial Utilisation Surveillance Program for 2015–19. Annual usage rates as a proportion were determined using the WHO AWaRe and Australian PAL categorization systems.

Results

In 2019, 70.0% of total-hospital aggregate antibacterial use in Australian acute-care hospitals fell into the WHO Access category, with 29.4% of usage in Watch and 0.6% in the Reserve category. Analysis using the PAL classification system showed 40.1% of hospital usage fell into the Access category, 55.6% in Curb and 3.8% in the Contain categories. On average, cefazolin usage comprised 12.5% of acute hospital usage.

Conclusions

Cefazolin, a first-line agent for surgical prophylaxis in Australia, was identified as a key antibacterial driving the differing results seen between the two classification systems. Data on the proportions of day surgery relative to inpatient surgical cases would assist the accuracy of benchmarking usage between hospitals using the PAL categorization system. The use of a targeted, nationally approved prioritized classification system can provide a focus for antimicrobial stewardship at a national level, however a clear understanding of the consumption metric used, as well as its limitations, are required for interpretation.
Workflow analysis for design of an electronic health record-based tobacco cessation intervention in community health centers
Authors: Gibson Bryan , Kramer Heidi , Weir Charlene , Fiol Guilherme , Borbolla Damian , Schlechter Chelsey R , Lam Cho , Nelson Marci , Bohner Claudia , Schulthies Sandra , Sieperas Tracey , Pruhs Alan , Nahum-Shani Inbal , Fernandez Maria E , Wetter David W
Published: February 2021

Objective

Tobacco use is the leading cause of preventable morbidity and mortality in the United States. Quitlines are effective telephone-based tobacco cessation services but are underutilized. The goal of this project was to describe current clinical workflows for Quitline referral and design an optimal electronic health record (EHR)-based workflow for Ask-Advice-Connect (AAC), an evidence-based intervention to increase Quitline referrals.

Materials and methods

Ten Community Health Center systems (CHC), which use three different EHRs, participated in this study. Methods included: 9 group discussions with CHC leaders; 33 observations/interviews of clinical teams' workflow; surveys with 57 clinical staff; and assessment of the EHR ecosystem in each CHC. Data across these methods were integrated and coded according to the Fit between Individual, Task, Technology and Environment (FITTE) framework. The current and optimal workflow were notated using Business Process Modelling Notation. We compared the requirements of the optimal workflow with EHR capabilities.

Results

Current workflows are inefficient in data collection, variable in who, how, and when tobacco cessation advice and referral are enacted, and lack communication between referring clinics and the Quitline. In the optimal workflow, medical assistants deliver a standardized AAC intervention during the visit intake. Referrals are submitted electronically, and there is bidirectional communication between the clinic and Quitline. We implemented AAC within all three EHRs; however, deviations from the optimal workflow were necessary.

Conclusion

Current workflows for Quitline referral are inefficient and ineffective. We propose an optimal workflow and discuss improvements in EHR capabilities that would improve the implementation of AAC.
Differences and similarities between the impact of the first and the second COVID-19-lockdown on mental health and safety behaviour in Germany
Authors: Moradian Sheila , Bäuerle Alexander , Schweda Adam , Musche Venja , Kohler Hannah , Fink Madeleine , Weismüller Benjamin , Benecke Anke-Verena , Dörrie Nora , Skoda Eva-Maria , Teufel Martin
Published: February 2021

Background

Governmental restrictions of daily life are key elements in reducing the transmission of COVID-19, but they have also put a strain on people’s mental health. Preventive policies differ all over the world as well as over different periods of time, and depend mostly on current infection rates. In Germany, there were two periods of restraint of varying severity, during which the government used different combinations of containment and mitigation measures to protect risk groups and to lower the number of hospitalizations.

Methods

In two online studies, we aimed to determine differences and similarities in COVID-19-related fear, generalized anxiety, depression and distress levels, as well as in the adherence to safety behaviour between the first lockdown in March and April and the second lockdown in November.

Results

This study showed continued high psychological burden and even increased levels of depression symptoms, as well as less safety behaviour in the second phase of restrictions.

Conclusions

The results hint at a prolonged negative impact on people’s mental health and their safety behaviour despite lesser restrictions in the second lockdown, which may be interpreted as pandemic fatigue and hence strengthens the argument for a low-threshold access to psychological care.
The nature of beneficiaries’ rights—can there be a trust to observe a licence over property?
Authors: Wilde David
Published: February 2021

This article considers the nature of a trust beneficiary’s rights. Specifically, it challenges a body of academic opinion that suggests it is not possible for a trust to exist where the only benefit conferred by the trust’s terms on its beneficiary is that the trustee must observe a licence for the beneficiary to use the trust property, given that a licence is only a personal right not a property interest.
Risk Factors for Severe COVID-19 in Children
Authors: Graff Kelly , Smith Christiana , Silveira Lori , Jung Sarah , Curran-Hays Shane , Jarjour Jane , Carpenter Lauren , Pickard Kasey , Mattiucci Michael , Fresia JoEllen , McFarland Elizabeth J. , Dominguez Samuel R. , Abuogi Lisa
Published: February 2021

Background:

There are limited pediatric data regarding severe COVID-19 disease. Our study aims to describe the epidemiology and identify risk factors for severe COVID-19 disease in children.

Methods:

This is a retrospective cohort study among children with positive SARS-CoV-2 PCR from March to July 2020 at Children’s Hospital Colorado. Risk factors for severe disease were analyzed as defined by hospital admission, respiratory support, or critical care. Univariable and multivariable analyses were conducted.

Results:

Among 454 patients identified with SARS-CoV-2, 191 (42.1%) were females, median age 11 years. Fifty-five percent of all patients identified as Hispanic compared with 29% among all hospital visits in 2019 (P < 0.0001). In multivariable analyses, age 0–3 months or >20 years [adjusted odds ratio (aOR), 7.85; P < 0.0001 and aOR, 5.1; P = 0.03, respectively], preterm birth history (aOR, 3.7; P = 0.03), comorbidities [including immunocompromise (aOR, 3.5; P = 0.004), gastrointestinal condition (aOR, 2.7; P = 0.009), diabetes (aOR, 6.6; P = 0.04), asthma (aOR, 2.2; P = 0.04)], and specific symptoms at presentation were predictors for admission. Age 0–3 months or >20 years, asthma, gastrointestinal condition, and similar symptoms at presentation were also predictors for respiratory support. Elevated C-reactive protein was associated with the need for critical care with median of 17.7 mg/dL (IQR, 5.3–22.9) versus 1.95 mg/dL (IQR, 0.7–5.5) among patients requiring critical versus no critical care (OR, 1.2; P = 0.02).

Conclusions:

Extremes of age, comorbid conditions, and elevated CRP are predictors of severe disease in children. Findings from this study can inform pediatric providers and public health officials to tailor clinical management, pandemic planning, and resource allocation.
Repositioning surgery of different intraocular lens designs in eyes with late in-the-bag intraocular lens dislocation
Authors: Dalby Marius , Drolsum Liv , Kristianslund Olav
Published: February 2021

Purpose:

To evaluate the long-term efficacy and safety after intraocular lens (IOL) repositioning by scleral suturing of 1-piece IOL compared with other IOL designs in the treatment of late in-the-bag IOL dislocation.

Setting:

Patients referred to Oslo University Hospital Oslo, Norway.

Design:

Prospective cohort study.

Methods:

The study comprised 54 patients (54 eyes) with late in-the-bag IOL dislocation treated with IOL repositioning by scleral sutures (10-0 polypropylene). All operations were performed with an anterior approach and by 1 surgeon. The following IOL designs were repositioned: 1-piece foldable (n = 17), 3-piece foldable (n = 28), plate-haptic (n = 8), and 1-piece rigid (n = 1) IOLs. Patients were evaluated comprehensively preoperatively and at 6 months (80%), 1 year (67%), and 2 years (61%) postoperatively. The main outcome measures were efficacy regarding corrected distance visual acuity (CDVA) and spherical equivalent (SE) and safety regarding complications.

Results:

Postoperative visual acuity was similar for different IOL designs. The mean SE change to final observation was −0.08 (95% CI, −0.93 to 0.77) in the 1-piece IOL group (n = 11) and −0.98 (−1.73 to −0.23) in the 3-piece IOL group (n = 18) (P = .11). Regarding safety, no patients had uveitis–glaucoma–hyphema syndrome, retinal detachment, or endophthalmitis. The 3-piece IOL group had 1 case of redislocation and 1 case of iritis. No patients had symptoms related to clinical IOL decentration. Long-term intraocular pressure remained within normal limits with overlapping 95% CIs for different IOLs.

Conclusions:

Repositioning surgery of 1-piece IOLs seems as efficient and safe as that for other IOL designs in the treatment of late in-the-bag IOL dislocation.
In vitro study examining the effectiveness of antiseptic prophylaxis for antibiotic-resistant bacterial endophthalmitis
Authors: O'Rourke Micheal , Knowles Susan J. , Curry Anya , Kealy Nikita , Barry Peter , Khan Rizwana
Published: February 2021

Purpose:

To assess the effectiveness of current antiseptic agents on multidrug-resistant (MDR) isolates in an in vitro setting.

Setting:

Department of Microbiology, The National Maternity Hospital, Dublin, Ireland.

Design:

Organisms were selected based on current review of endophthalmitis literature: methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, carbapenem-resistant and extended-spectrum β-lactamase Klebsiella pneumoniae, and vancomycin-resistant (VRE) Enterococcus faecalis.

Methods:

Samples were exposed to povidone–iodine (PVI) 5% and chlorhexidine (CHX) 0.05% for 0.5 minutes, 1 minute, 3 minutes, and 5 minutes. After inactivation, organisms were incubated under standard conditions and growth assessed after 16 hours.

Results:

MRSA and MRSE responded to 3-minute PVI exposure. CHX eradicated MRSA growth after 5 minutes but failed to completely suppress MRSE. Pseudomonas and Klebsiella required 3-minute CHX exposure and 5-minute PVI exposure for complete clearance. Eradication of enterococci (VRE positive and negative) was not achieved at 10 minutes of CHX or PVI exposure. Comparison of PVI vs CHX showed a benefit for PVI in MRSA (P < .01) and MRSE (P < .001) eradication at 3 minutes.

Conclusions:

Current recommendations of 3 minutes of antisepsis prior to intraocular surgery are not sufficient for complete eradication of MDR organisms from the ocular surface. A bespoke approach is suggested to patients at risk for carriage of MDR organisms to minimize the risk of endophthalmitis.
Can You Escape Sepsis? Using a Healthcare Escape Room as an Innovative Approach to Nursing Education
Authors: Dacanay Adrian P. , Sibrian Julia , Wyllie Colleen , Sorrentino Elizabeth , Dunbar Ghada
Published: February 2021

Purpose/Objectives

The purpose of this article is to provide the clinical nurse specialist with an interactive, creative, and fun approach using an escape room to increase the retention and application of knowledge about caring for patients with sepsis and improve patient care outcomes.

Description of the Project

This project involved the design of a healthcare-based escape room, where clinical nurses and interprofessional learners engaged in a series of puzzles and problem-solving experiences to apply clinical judgment and critical thinking about patient care.

Theory and Frameworks

Knowles' theory of adult learning guided the development of this gamified learning.

Outcome

The clinical nurse specialist was critical to the success of the escape room. The escape room created an innovative learning environment, expanding opportunities to engage staff and promote high-quality care for best patient outcomes.

Conclusion

The benefits of incorporating adult learning principles with gamification-based education as a teaching strategy are evident in the feedback and overwhelmingly positive responses received from participants. The successes of the sepsis escape room have presented opportunities to continue supporting progressive, fun, and evidence-based learning environments and positively impact both nursing education and patient care outcomes.
“Effect of the intervention with omega-3 fatty acids on nutritional and clinical aspects in patients with breast cancer receiving medical treatment”
Authors: Edgardo Palma-Gutierrez , Erika Espinoza-Rado , Jessica Hanae Zafra-Tanaka
Published: February 2021

Background

It is known that cancer can cause loss of body weight and muscle protein wasting, which leads to a state of malnutrition, which in turn worsens the prognosis and health of the cancer patient. It has been suggested that the promoting mechanism of this state is systemic inflammation, for which reason several clinical trials have used omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as adjuvants to antineoplastic treatment, mainly due to its anti-inflammatory effects. However, few systematic reviews and meta-analyzes have analyzed the effects of omega-3s in patients with breast cancer.

Objective

The aim of this study is to assess the effect of the supplementation with omega-3 fatty acids on nutritional and clinical outcomes in patients with breast cancer receiving medical treatment.

Methods

A systematic review will be conducted, starting with a search in PubMed, CENTRAL and EMBASE using search terms related to omega-3 fatty acids and breast cancer. We will include only randomized controlled trials that assess the effects of omega-3 in patients with breast cancer receiving medical treatment.. Data will be extracted in a spread sheet. Study selection and data extraction will be conducted by two reviewers independently and the Cochrane Risk of Bias Tool for RCT will be used for assessment of risk of bias. Discrepancies will be reviewed with a third reviewer.

Conclusion

This systematic review aims to provide an analysis on the outcomes of the usage of the intervention with omega-3 fatty acids on nutritional and clinical aspects in patients with breast cancer receiving medical treatment.
Place of preperitoneal pelvic packing in severe pelvic traumatisms: About 20 cases performed in a French military level one trauma center
Authors: Julie Hardy , Marie Coisy , Tristan Monchal , Stéphane Bourguoin , Thibaut Long Depaquit , Paul Chiron , Cardinale Mickael , Emmanuel Hornez , Paul Balandraud , Pierre-Henri Savoie
Published: February 2021

Background

The overall mortality of hemodynamically unstable pelvic fractures is high. Hemorrhage triggers off the Moore lethal triad. Hemostatic management during the golden hour is essential. Combined with pelvic stabilisation, preperitoneal pelvic packing (PPP) is proposed to control venous and bony bleeding, while arterioembolisation can stop arterial bleeding. No international consensus has yet prioritized these procedures. The aim of this study was to analyse a serie of PPP in a military level one trauma center and propose an algorithm for hemodynamically unstable pelvic traumas regardless of the military facility.

Method

From January 2010 to December 2020, every patient from our military institution with a hemodynamically unstable pelvic fracture underwent PPP combined with pelvic stabilisation. Before 2012 data were retrospectively collected from database (PMSI), after 2012 data were prospectively recorded in our polytrauma database and retrospectively analysed. The care algorithm applied focused on hemodynamic status of polytraumatised patients on admission. Primary criteria were early hemorrhage-induced mortality (<24h) and overall mortality (<30d). Secondary criteria were systolic blood pressure (SBP) and red blood cells (RBC) units administered.

Results

20 patients with a pelvic fracture had a PPP. Mean age was 49,65 +/-23,97 years and median ISS was 49 (31; 67). The decrease of blood transfusion and increase of SBP between pre- and postoperative values were statistically significant. Eight patients (40%) had postoperative arterial pelvic blush and 7 patients were embolised. The early mortality by refractory hemorrhagic shock was 25% (5/20). Overall mortality at 30 days was 50% (10/20).

Conclusion

PPP is a quick, easy, efficient and safe procedure. It can control venous, bony and sometimes arterial bleeding. PPP is part of damage control surgery and we propose it in first line. Angio-embolization remains complementary. Besides, PPP is the only means available in precarious conditions of practice, notably in military forward units.
CLINICAL PERFORMANCE OF THE CALL SCORE FOR THE PREDICTION OF ADMISSION TO ICU AND DEATH IN HOSPITALIZED PATIENTS WITH COVID-19 PNEUMONIA IN A REFERENCE HOSPITAL IN PERU
Authors: Pichardo-Rodriguez Rafael , Saavedra-Velasco Marcos , Peña-Oscuvilca Willy , Ascarza-Saldaña Jhonnathan , Sanchez-Alvarez Cesar , Patron-Ordoñez Gino , Ruiz-Franco Oscar , De La Cruz-Vargas Jhony A. , Garcia-Perdomo Herney Andres
Published: February 2021

Objective

Determine the CALL SCORE’s diagnostic accuracy for the prediction of ICU admission and death in patients hospitalized for COVID-19 pneumonia in a reference hospital in Peru.

Methods

We performed an analytical cross-sectional observational study. We included patients with COVID-19 pneumonia treated at the “Dos de Mayo” National Hospital. Patients over 18 years old with a diagnosis confirmed by rapid or molecular testing were included. Those with an incomplete, illegible, or missing medical history and/or bacterial or fungal pneumonia were excluded. Data were extracted from medical records. The primary outcomes were mortality and admission to the ICU. The Call Score was calculated for each patient (4 to 13 points) and classified into three risk groups. Summary measures were presented for qualitative and quantitative variables. The area under the model curve and the operational characteristics (sensitivity, specificity) were calculated for the best cut-off point.

Results

The Call Score reported an area under the curve of 0.59 (IC95%: 0.3 to 0.07), p = 0.43 for predicting death. However, for a cut-off point of 5.5, a sensitivity of 87%and a specificity of 65%were obtained. The area under the curve for ICU admission was 0.67 (95%CI: 0.3 to 0.07), p = 0.43; the 5.5 cut-off point showed a sensitivity of 82%and a specificity of 51%.

Conclusions

The Call Score shows a low performance for predicting mortality and admission to the ICU in Peruvian patients.
Quantitative genome-scale analysis of human liver reveals dysregulation of glycosphingolipid pathways in progressive nonalcoholic fatty liver disease
Authors: Sen Partho , Govaere Olivier , Sinioja Tim , McGlinchey Aidan , Geng Dawei , Ratziu Vlad , Bugianesi Elisabetta , Schattenberg Jörn M. , Vidal-Puig Antonio , Allison Michael , Cockell Simon , Daly Ann K. , Hyötyläinen Tuulia , Anstee Quentin M. , Orešič Matej
Published: February 2021

Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease that is associated with multiple metabolic disturbances, yet the metabolic pathways underlying its progression are poorly understood. Here we studied metabolic pathways of the human liver across the full histological spectrum of NAFLD. We analyzed whole liver tissue transcriptomics and serum metabolomics data obtained from a large, prospectively enrolled cohort of 206 histologically characterized patients derived from the European NAFLD Registry and developed genome-scale metabolic models (GEMs) of human hepatocytes at different stages of NAFLD. We identified several metabolic signatures in the liver and blood of these patients, specifically highlighting the alteration of vitamins (A, E) and glycosphingolipids, and their link with complex glycosaminoglycans in advanced fibrosis. Furthermore, we derived GEMs and identified metabolic signatures of three common NAFLD-associated gene variants(PNPLA3, TM6SF2andHSD17B13). The study demonstrates dysregulated liver metabolic pathways which may contribute to the progression of NAFLD.
Distinct gut and vaginal microbiota profile in women with Recurrent Implantation Failure and Unexplained Infertility
Authors: Patel Nayna , Patel Nidhi , Pal Sejal , Nathani Neelam , Pandit Ramesh , Patel Molina , Patel Niket , Joshi Chaitanya , Parekh Bhavin
Published: February 2021

Background

Implantation failure limits the success rate of natural and in vitro fertilization (IVF)-assisted conceptions. Evidence suggests dysbiosis in the female reproductive tract impacts implantation failure. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains unexplored.

Method

We recruited 11fertile women as the controls, and a cohort of 20 women diagnosed with implantation-failure associated infertility, which included 10 women diagnosed with recurrent implantation failure (RIF), and 10 women diagnosed with unexplained infertility (UE). Using next-generation amplicon sequencing, we compared the diversity, structure, and composition of fecal and vaginal bacteria of the controls with that of the infertile cohort. While we sequenced fecal samples of all the participants (n=31), we could only sequence 8 vaginal samples in each group (n=24).

Results

Compared with the controls, α-diversity of the gut bacteria, analysed by Chao 1 and Shannon indices, among the infertile groups declined (p□<□0.05). β-diversity between the controls and infertile cohort, measured by both Bray-Curtis and Jaccard distances, differed significantly (p□<□0.05). Taxa analysis of the gut bacteria revealed enrichment of Gram-positive bacteria, mainly of the phylum Firmicutes, in the RIF group. In contrast, Gram-negative bacteria were relatively more abundant in the UE group. Additionally, mucus-producing bacteria genera such as Prevotella and Sutterella declined in the infertile cohort (p□<□0.05). Intriguingly, significant enrichment (p□<□0.05) of the genus Hungatella, associated with trimethylamine N-oxide (TMAO) production, occurred in the infertile cohort. Vaginal microbiota was dominated by L. iners across the groups, with the UE group showing the highest levels. Of the three groups, the RIF group had the least diverse vaginal microbiota. Taxa analysis showed higher levels of anaerobic bacteria such as Leptotrichia, Snethia, and Prevotella in the controls.

Conclusion

We posit that in the setting of the compromised gut mucosal barrier, the phyla Firmicutes generates TNF-α-driven systemic inflammation, leading to RIF, whereas an overload of Gram-negative bacteria induces IL-6-driven systemic inflammation, leading to UE. Additionally, Hungatella-induced elevation of TMAO levels causes platelet hypercoagulability, synergistically contributing to implantation failure. Finally, vaginal dysbiosis does not appear to co-occur with gut dysbiosis.
Diet-dependentNatriuretic Peptide Receptor Cexpression in adipose tissue is mediated by PPARγ via long-range distal enhancers
Authors: Shi Fubiao , Simandi Zoltan , Nagy Laszlo , Collins Sheila
Published: February 2021

In addition to their established role to maintain blood pressure and fluid volume, the cardiac natriuretic peptides (NPs) can stimulate adipocyte lipolysis and control the brown fat gene program of nonshivering thermogenesis. The NP “clearance” receptor C (NPRC) functions to clear NPs from the circulation via peptide internalization and degradation and thus is an important regulator of NP signaling and adipocyte metabolism. It is well appreciated that theNprcgene is highly expressed in adipose tissue and is dynamically regulated with nutrition and environmental changes. However, the molecular basis for howNprcgene expression is regulated is still poorly understood. Here we identified Peroxisome Proliferator-Activated Receptor gamma (PPARγ) as a transcriptional regulator ofNprcexpression in mouse adipocytes. During 3T3-L1 adipocyte differentiation, levels ofNprcexpression increase in parallel with PPARγ induction. Rosiglitazone, a classic PPARγ agonist, increases, while siRNA knockdown of PPARγ reduces,Nprcexpression in 3T3-L1 adipocytes. We demonstrate that PPARγ controlsNprcgene expression in adipocytes through its long-range distal enhancers. Furthermore, the induction ofNprcexpression in adipose tissue during high-fat diet feeding is associated with increased PPARγ enhancer activity. Our findings define PPARγ as a mediator of adipocyteNprcgene expression and establish a new connection between PPARγ and the control of adipocyte NP signaling in obesity.