bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Sessile Serrated Adenoma Detection Rate With Mechanical New Technology Devices
Authors: Verheyen Elijah , Castaneda Daniel , Gross Seth A. , Popov Violeta
Published: July 2020

Goal:

This meta-analysis aims to compare the sessile-serrated adenoma detection rate (SSADR) of currently available mechanical new technology devices (NTDs) to conventional colonoscopy (CC).

Background:

NTDs including Endocuff, EndoRing, G-Eye, and AmplifEYE were developed with the aim of improving adenoma detection rate by enhancing colonic mucosal visualization. Increasing awareness of the risk of sessile-serrated adenoma progression to malignancy has ushered a need to increase the detection of these characteristically flat lesions.

Study:

Embase and PubMed/Medline databases were searched from inception through January 2019 for published manuscripts or major conference abstracts reporting SSADR with Endocuff, EndoRing, G-Eye, AmplifEYE, and CC. Randomized controlled trials, high-quality case-control, cohort, and observational studies in adults with >10 subjects were included. The primary outcome was pooled SSADR odds ratio (ORs) with 95% confidence interval (95% CI) comparing CC with the NTDs. In addition, an analysis comparing each device to CC was performed.

Results:

Of 207 citations identified, a total of 14 studies with 12,655 subjects were included in our analysis (5931 subjects with NTDs and 6724 with CC). There were 12 studies with Endocuff, 2 with EndoRing, 1 with G-EYE, and 1 with AmplifEYE. The mean age was 62.4 years and 57.5% were males. Pooled SSADR with NTDs was 12.3% as compared with 6.4% with CC, with an OR of 1.81 (95% CI: 1.6-2.0, I
2: 77%). Analysis of Endocuff alone yielded an OR 1.81 (95% CI: 1.6-2.1, I
2: 79%).

Conclusion:

Mechanical NTDs, notably Endocuff, are a safe and effective tool to increase the SSADR.
Incidence Rates, Treatment, and Survival of Rectal Cancer Among Young Patients
Authors: Ramai Daryl , Ofosu Andrew , Solanki Vaibhavi , Lai Jonathan K. , Barakat Mohamed , Dhaliwal Amaninder , Aamar Ali , Aloreidi Khalil , Mohan Babu P. , Reddy Madhavi , Adler Douglas G.
Published: July 2020

Background:

The incidence of colorectal cancer is increasing among young adults in the United States. We aim to investigate the incidence rate, the effect of multimodal therapy, and survival outcomes of rectal cancer in patients under 45 years of age.

Patients and Methods:

Data on young-onset (under 45 y) rectal cancer between 2000 and 2016 was extracted from the Surveillance, Epidemiology, and End Results Registry (SEER).

Results:

A total of 10,375 patients with young-onset rectal cancer were identified where 54.7% were male. The median age at diagnosis was 40±5.7 years. The overall age-adjusted incidence of rectal cancer between 2000 and 2016 was 1.24 per 100,000 per year. Incidence increased with age, with the highest incidence occurring in the 40- to 44-year age group. Over the 16-year study period, rectal cancer increased by ∼2.29%. Most tumors on presentation were moderately differentiated (30.8%) while the most common stage at presentation was stage 4 (48.3%). One- and 5-year cause-specific survival for rectal cancer was 93% and 72%, respectively. According to Cox proportional hazard models, chemotherapy was associated with increased mortality in patients with localized cancer [hazard ratio (HR)=2.88, 95% confidence interval (CI): 2.04-4.08, P<0.001], did not significantly improve mortality outcomes in patients with regional cancer (HR=0.89, 95% CI: 0.70-1.04, P=0.116), but reduced mortality in patients with distant cancer (HR=0.62, 95% CI: 0.56-0.70, P<0.001), though this effect was largely seen in patients 35 years and older. Surgery was associated with improved survival across all cancer stages.

Conclusions:

The incidence of regional and distant rectal cancer is increasing in young patients. While patient age is an important prognostic indicator of survival, chemotherapy does not appear to improve survival in younger patients with localized and regional disease.
Coexisting Abnormal Esophageal Body Motility Predicts Clinical Symptoms and Bolus Transit in Patients With Esophagogastric Junction Outflow Obstruction (EGJOO)
Authors: Jodorkovsky Daniela , Wong Danny , Din Ryan , Sikavi Daniel R. , Lee Darren J.H. , Cai Jennifer X. , Lo Wai-Kit , Chan Walter W.
Published: July 2020

Goal:

The goal of this study was to compare the clinical presentations of esophagogastric junction outflow obstruction (EGJOO) with coexisting abnormal esophageal body motility (EBM) to isolated EGJOO.

Background:

The clinical significance and management of EGJOO remain debated, as patients may have varied to no symptoms. The effect of coexisting abnormal EBM in EGJOO is unclear. We hypothesized that a concomitant EBM disorder is associated with clinical symptoms of EGJOO.

Study:

This was a retrospective cohort study of consecutive adults diagnosed with EGJOO on high-resolution impedance-manometry (HRIM) at 2 academic centers in March 2018 to September 2018. Patients with prior treatment for achalasia, foregut surgery, or evidence of obstruction were excluded. Subjects were divided into EGJOO with abnormal EBM per Chicago classification v3.0 and isolated EGJOO. Statistical analyses were performed using Fisher-exact or Student t test (univariate) and logistic or linear regression (multivariate).

Results:

Eighty-two patients (72% women, age 61.1±10.7 y) were included. Thirty-one (37.8%) had abnormal EBM, including 16 (19.5%) ineffective esophageal motility and 15 (18.2%) hypercontractile esophagus. Esophageal symptoms (heartburn, regurgitation, chest pain, dysphagia) were more prevalent among those with abnormal EBM (90.3% vs. 64.7%, P=0.01). On logistic regression adjusting for age, gender, body mass index, and opioid use, abnormal EBM remained predictive of esophageal symptoms (adjusted odds ratio [aOR] 7.51, P=0.007). On separate models constructed, HE was associated with chest pain (aOR 7.45, P=0.01) and regurgitation (aOR 4.06, P=0.046), while ineffective esophageal motility was predictive of heartburn (aOR 5.84, P=0.009) and decreased complete bolus transit (β-coefficient −0.177, P=0.04).

Conclusion:

Coexisting abnormal EBM is associated with esophageal symptoms and bolus transit in patients with EGJOO.
Outcomes and Predictors of Wound Healing among Patients with Complex Diabetic Foot Wounds Treated with a Dermal Regeneration Template (Integra)
Authors: Hicks Caitlin W. , Zhang George Q. , Canner Joseph K. , Mathioudakis Nestoras , Coon Devin , Sherman Ronald L. , Abularrage Christopher J.
Published: July 2020

Background:

The utility of dermal regeneration templates for treating high-risk diabetic foot wounds is unclear. The authors report wound healing and major amputation outcomes among a cohort of diabetic patients with complex diabetic foot wounds treated in a multidisciplinary setting.

Methods:

All patients with complex diabetic foot wounds treated with a dermal regeneration template (March of 2013 to February of 2019) were captured in a prospective institutional database. Wound severity was classified according to the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system to determine limb salvage prognosis at baseline. Wound healing and major amputation rates were reported using Kaplan-Meier analyses. A stepwise Cox proportional hazards model was used to identify independent characteristics associated with wound healing.

Results:

Eighty-five patients with 107 complex diabetic foot wounds were treated (mean age, 61.2 ± 3.3 years; 63.5 percent male and 61.2 percent African American). Most diabetic foot wounds were high-risk (wound, ischemia, and foot infection stage 3 or 4, 93.5 percent), corresponding to a predicted 25 to 50 percent risk of major amputation at 1 year. Dermal regeneration template use resulted in successful wound granulation in 66.7 percent of cases, with a mean time to complete wound healing of 198 ± 18 days. Twelve- and 18-month wound healing rates were 79.0 ± 5.0 percent and 93.0 ± 3.3 percent, respectively. Major amputation was required in 11.2 percent of patients. Independent predictors of poor wound healing included lack of bone involvement, higher WIfI stage, and prior dermal regeneration template failure.

Conclusion:

Application of a dermal regeneration template to complex diabetic foot wounds at high risk for major amputation results in good wound healing and excellent limb salvage outcomes among diabetic patients treated in a multidisciplinary setting.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
High HIV Prevalence and Low HIV-Service Engagement Among Young Women Who Sell Sex: A Pooled Analysis Across 9 Sub-Saharan African Countries
Authors: Rucinski Katherine B. , Schwartz Sheree R. , Mishra Sharmistha , Phaswana-Mafuya Nancy , Diouf Daouda , Mothopeng Tampose , Kouanda Seni , Simplice Anato , Kouame Abo , Cham Bai , Tamoufe Ubald , Matse Sindy , Hausler Harry , Fouda Ghislaine , Pitche Vincent , Baral Stefan D.
Published: July 2020

Background:

Epidemiological data are needed to characterize the age-specific HIV burden and engagement in HIV services among young, marginalized women in sub-Saharan Africa.

Setting:

Women aged ≥18 years who reported selling sex were recruited across 9 countries in Southern, Central, and West Africa through respondent driven sampling (N = 6592).

Methods:

Individual-level data were pooled and age-specific HIV prevalence and antiretroviral therapy (ART) coverage were estimated for each region using generalized linear mixed models. HIV-service engagement outcomes (prior HIV testing, HIV status awareness, and ART use) were compared among women living with HIV across age strata (18–19, 20–24, and ≥25 years) using generalized estimating equations.

Results:

By age 18%–19%, 45.4% [95% confidence interval (CI): 37.9 to 53.0], 5.8% (95% CI: 4.3 to 7.8), and 4.0% (95% CI: 2.9 to 5.4) of young women who sell sex were living with HIV in Southern, Central, and West Africa respectively. Prevalence sharply increased during early adulthood in all regions, but ART coverage was suboptimal across age groups. Compared with adult women ≥25, young women aged 18–19 were less likely to have previously tested for HIV [prevalence ratio (PR) 0.76; 95% CI: 0.72 to 0.80], less likely to already be aware of their HIV status (PR 0.48; 95% CI: 0.35 to 0.64), and less likely to be taking ART (PR 0.67; 95% CI: 0.59 to 0.75).

Conclusions:

HIV prevalence was already high by age 18–19 in this pooled analysis, demonstrating the need for prevention efforts that reach women who sell sex early in their adolescence. ART coverage remained low, with women in the youngest age group the least engaged in HIV-related services. Addressing barriers to HIV service delivery among young women who sell sex is central to a comprehensive HIV response.
Aspergillus fumigatus and pan-azole resistance: who should be concerned?
Authors: Wiederhold Nathan P. , Verweij Paul E.
Published: July 2020

Purpose of review

Although clinical outcomes in the treatment of aspergillosis have markedly improved with the availability of newer triazoles, the development of resistance to these antifungals, especially in Aspergillus fumigatus, is a growing concern. The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis.

Recent findings

Resistance may develop through either patient or environmental azole exposure. Environmental exposure is the most prevalent means of resistance development, and these isolates can cause disease in various at-risk groups, which now include those with influenza, and potentially COVID-19. Although current treatment options are limited, newer therapies are in clinical development. These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus.

Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. Certain geographic regions and patient populations appear to be at increased risk for this pathogen. As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. While treatment options are currently limited, new agents under clinical development may offer hope.
EEG Findings and Releases From Hospital for Patients With Anti-NMDA Receptor Encephalitis
Authors: Gómez Ávila Felipe Alberto , González-Aragón Maricarmen Fernández , Avellán Álvaro Moreno , San-Juan Daniel
Published: July 2020

Purpose:

Anti-N-methyl-D-aspartate receptor encephalitis is produced by an autoimmune reaction against macromolecular structures that form ionotropic receptors for glutamic acid NR2A and NR2B subunits. Other important findings are the multiple clinical and paraclinical manifestations, among which the EEG stands out. We characterized EEG patterns and their association with functional disability and hospitalization time in patients with anti-N-methyl-D-aspartate receptor encephalitis admitted in our center.

Methods:

We performed a retrospective cohort study that included patients with anti-N-methyl-D-aspartate receptor encephalitis. We recorded the clinical and sociodemographic characteristics and initial scalp EEG data. Functional disability was evaluated at admission and follow-up using the modified Rankin scale.

Results:

Forty-five patients aged 15 to 80 years were included. An abnormal EEG was reported in 92.5% of patients. We identified six EEG patterns. The mean hospitalization time was 3.2 (±2.4) months. The higher modified Rankin scale at admission and the absence of parietal or temporal epileptiform activity were associated with more prolonged hospitalization, hazard ratio of 0.338 for each modified Rankin scale level (95% confidence interval 0.174–0.658, P = 0.001), 14.5, P = 0.017, and hazard ratio of 5.6, P = 0.009, respectively.

Conclusions:

EEGs are frequently abnormal in patients with anti-N-methyl-D-aspartate receptor encephalitis. The lower modified Rankin scale at admission and the absence of some focal epileptiform activity may be associated with shorter hospitalizations.
No evidence for individual recognition in threespine or ninespine sticklebacks (
Gasterosteus aculeatus
or
Pungitius pungitius
)
Authors: Webster Mike M. , Laland Kevin N.
Published: July 2020

Recognition plays an important role in the formation and organization of animal groups. Many animals are capable of class-level recognition, discriminating, for example, on the basis of species, kinship or familiarity. Individual recognition requires that animals recognize distinct cues, and learn to associate these with the specific individual from which they are derived. In this study, we asked whether sticklebacks (
Gasterosteus aculeatus
and
Pungitius pungitius
) were capable of learning to recognize individual conspecifics. We have used these fish as model organisms for studying selective social learning, and demonstrating a capacity for individual recognition in these species would provide an exciting opportunity for studying how biases for copying specific individuals shape the dynamics of information transmission. To test for individual recognition, we trained subjects to associate green illumination with the provision of a food reward close to one of two conspecifics, and, for comparison, one of two physical landmarks. Both species were capable of recognizing the rewarded landmark, but neither showed a preference for associating with the rewarded conspecific. Our study provides no evidence for individual recognition in either species. We speculate that the fission–fusion structure of their social groups may not favour a capacity for individual recognition.
Preparation of polyacrylonitrile-based fibres with chelated Ag ions for antibacterial applications
Authors: Chang Li , Duan Wenjie , Chen Anguo , Li Jianjun , Huang Siqi , Tang Huijuan , Pan Gen , Deng Yong , Zhao Lining , Li Defang , Zhao Liang
Published: July 2020

The need for an excellent antibacterial material that is sufficiently powerful to never develop bacterial resistance is urgent. In this study, a series of novel polyacrylonitrile-based fibres with chelated Ag ions (referred to as Ag-SH-PANF) were prepared by a two-step chemical modification process: grafting and chelating. The properties of the as-prepared Ag-SH-PANF were characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The antibacterial activities of Ag-SH-PANF were examined against pathogenic bacteria, and an antibacterial mechanism was explicated based on the release of Ag ions from the fibres' surfaces. The results showed that, although chelation occurred between the Ag ions and the grafted amino, sulfhydryl and disulfide groups, Ag-SH-PANF retained its fine microstructure and thermal stability. Moreover, Ag-SH-PANF displayed excellent antibacterial ability against pathogenic bacteria as well as good washing durability. In terms of the antibacterial mechanism, Ag ions are the main bactericidal agents in the role of catalysts and are not consumed in the antibacterial process. Nonetheless, a relatively higher concentration of Ag ions can accelerate the bactericidal process.
Predictors of mathematical attainment trajectories across the primary-to-secondary education transition: parental factors and the home environment
Authors: Evans Danielle , Field Andy P.
Published: July 2020

A ‘maths crisis’ has been identified in the UK, with many adults and adolescents underachieving in maths and numeracy. This poor performance is likely to develop from deficits in maths already present in childhood. Potential predictors of maths attainment trajectories throughout childhood and adolescence relate to the home environment and aspects of parenting including parent–child relationships, parental mental health, school involvement, home teaching, parental education and gendered play at home. This study examined the aforementioned factors as predictors of children's maths attainment trajectories (age 7–16) across the challenging transition to secondary education. A secondary longitudinal analysis of the Avon Longitudinal Study of Parents and Children found support for parental education qualifications, a harmonious parent–child relationship and school involvement at age 11 as substantial predictors of maths attainment trajectories across the transition to secondary education. These findings highlight the importance of parental involvement for maths attainment throughout primary and secondary education.
Hydrolysis-resistant and stress-buffering bifunctional polyurethane adhesive for durable dental composite restoration
Authors: Zhang Jiahui , Guo Xiaowei , Zhang Xiaomeng , Wang Huimin , Zhu Jiufu , Shi Zuosen , Zhu Song , Cui Zhanchen
Published: July 2020

A new elastic polyurethane (PU) adhesive was reported in this study to improve the stability and durability of the dental adhesion interface. A polyurethane oligomer was synthesized by the solution polymerization method, and a diluent and solvent were added to prepare PU adhesives. The water sorption, water solubility, contact angle, thermal stability, degree of conversion and mechanical properties of the PU adhesives were evaluated. Experimental applications for tooth restoration (microtensile bond strength and microleakage) were also performed, and cytotoxicity test was carried out. The water sorption and solubility of the PU adhesives were significantly lower than those of three commercial adhesives. The microtensile bond strength of the PU adhesives was improved after thermocycling test, and the extent of microleakage was diminished when compared with that of commercial adhesives. Biocompatibility testing demonstrated that the PU adhesive was non-toxic to L929 fibroblasts. This study shows the ability of PU adhesive to improve the stability and durability of the dental adhesion interface and may refocus the attention of scientists from rigid bonding to flexible bonding for dental adhesion, and it sheds light on a new strategy for the stable and durable bonding interface of dentine adhesives.
Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma
Authors: Kammoun Ahmed K. , Khedr Alaa , Khayyat Ahdab N. , Hegazy Maha A.
Published: July 2020

A parenteral medical combination containing vaborbactam and meropenem is used mainly to treat complicated urinary tract infections. A novel ultra-performance liquid chromatography tandem mass spectrometric method was developed for the sensitive determination of both compounds in human plasma. Sample preparation was performed by precipitation technique. The chromatographic separation was accomplished using the Acquity C18-BEH column, 0.01 M ammonium formate: acetonitrile (47 : 53, v/v) as a mobile phase with a flow rate of 0.2 ml min
−1
. Analytes were monitored by applying multiple reaction monitoring. The bioanalytical validation criteria were conducted following the Food and Drug Administration recommendations. The method was linear within range 0.5 to 50 µg ml
−1
, for both drugs. The intra-day and inter-day precision, as coefficient variation (% CV) and the accuracy, as % bias did not exceed 15% for both drugs. The percentage recovery of targeted analytes was not less than 77%, calculated at three quality control levels. The proposed method showed a suitable lower level of quantification value of 0.50 µg ml
−1
for both analytes, which is far lower than the expected
C
max
, which permits the use of this method for pharmacokinetic studies. The proposed method proved to be useful for the evaluation of this combination in both human plasma and pharmaceutical formulation.
Integrative taxonomy revisits the ontogeny and trophic niches ofRimicarisvent shrimps
Authors: Methou Pierre , Michel Loïc N. , Segonzac Michel , Cambon-Bonavita Marie-Anne , Pradillon Florence
Published: July 2020

Among hydrothermal vent species,Rimicaris exoculatais one of the most emblematic, hosting abundant and diverse ectosymbioses that provide most of its nutrition.Rimicaris exoculataco-occurs in dense aggregates with the much less abundantRimicaris chaceiin many Mid-Atlantic Ridge vent fields. This second shrimp also houses ectosymbiotic microorganisms but has a mixotrophic diet. Recent observations have suggested potential misidentifications between these species at their juvenile stages, which could have led to misinterpretations of their early-life ecology. Here, we confirm erroneous identification of the earliest stages and propose a new set of morphological characters unambiguously identifying juveniles of each species. On the basis of this reassessment, combined use of C, N and S stable isotope ratios reveals distinct ontogenic trophic niche shifts in both species, from photosynthesis-based nutrition before settlement, towards a chemosynthetic diet afterwards. Furthermore, isotopic compositions in the earliest juvenile stages suggest differences in larval histories. Each species thus exhibits specific early-life strategies that would, without our re-examination, have been interpreted as ontogenetic variations. Overall, our results provide a good illustration of the identification issues persisting in deep-sea ecosystems and the importance of integrative taxonomy in providing an accurate view of fundamental aspects of the biology and ecology of species inhabiting these environments.
Precipitation and vegetation shape patterns of genomic and craniometric variation in the central African rodent
Praomys misonnei
Authors: Morgan Katy , Mboumba Jean-François , Ntie Stephan , Mickala Patrick , Miller Courtney A. , Zhen Ying , Harrigan Ryan J. , Le Underwood Vinh , Ruegg Kristen , Fokam Eric B. , Tasse Taboue Geraud C. , Sesink Clee Paul R. , Fuller Trevon , Smith Thomas B. , Anthony Nicola M.
Published: July 2020

Predicting species' capacity to respond to climate change is an essential first step in developing effective conservation strategies. However, conservation prioritization schemes rarely take evolutionary potential into account. Ecotones provide important opportunities for diversifying selection and may thus constitute reservoirs of standing variation, increasing the capacity for future adaptation. Here, we map patterns of environmentally associated genomic and craniometric variation in the central African rodent
Praomys misonnei
to identify areas with the greatest turnover in genomic composition. We also project patterns of environmentally associated genomic variation under future climate change scenarios to determine where populations may be under the greatest pressure to adapt. While precipitation gradients influence both genomic and craniometric variation, vegetation structure is also an important determinant of craniometric variation. Areas of elevated environmentally associated genomic and craniometric variation overlap with zones of rapid ecological transition underlining their importance as reservoirs of evolutionary potential. We also find that populations in the Sanaga river basin, central Cameroon and coastal Gabon are likely to be under the greatest pressure from climate change. Lastly, we make specific conservation recommendations on how to protect zones of high evolutionary potential and identify areas where populations may be the most susceptible to climate change.
The ghost of disturbance past: long-term effects of pulse disturbances on community biomass and composition
Authors: Jacquet Claire , Altermatt Florian
Published: July 2020

Current global change is associated with an increase in disturbance frequency and intensity, with the potential to trigger population collapses and to cause permanent transitions to new ecosystem states. However, our understanding of ecosystem responses to disturbances is still incomplete. Specifically, there is a mismatch between the diversity of disturbance regimes experienced by ecosystems and the one-dimensional description of disturbances used in most studies on ecological stability. To fill this gap, we conducted a full factorial experiment on microbial communities, where we varied the frequency and intensity of disturbances affecting species mortality, resulting in 20 different disturbance regimes. We explored the direct and long-term effects of these disturbance regimes on community biomass. While most communities were able to recover biomass and composition states similar to undisturbed controls after a halt of the disturbances, we identified some disturbance thresholds that had long-lasting legacies on communities. Using a model based on logistic growth, we identified qualitatively the sets of disturbance frequency and intensity that had equivalent long-term negative impacts on experimental communities. Our results show that an increase in disturbance intensity is a bigger threat for biodiversity and biomass recovery than the occurrence of more frequent but less intense disturbances.
Does sub-culturing of positive MRSA blood cultures affect vancomycin MICs?
Authors: Kanesaka Izumo , Ito Takamitsu , Shishido Ritsuko , Nagashima Makoto , Kanayama Katsuse Akiko , Takahashi Hiroshi , Fujisaki Shingo , Kobayashi Intetsu
Published: July 2020

Introduction. Empirical vancomycin (VAN) treatment failure for methicillin-resistant

Staphylococcus aureus

(MRSA) bacteraemia, with significantly higher mortality, has been reported for MRSA strains with reduced VAN susceptibility.

Aim. Our goal was to study the effect of sub-culture on VAN minimum inhibitory concentration (MIC) values compared to direct susceptibility of MRSA-positive blood cultures.

Methodology. Using 19 MRSA-positive blood cultures and 19 seeded MRSA-positive blood cultures, we compared the VAN MICs from direct susceptibility testing of MRSA-positive blood cultures and MRSA sub-cultured from positive blood cultures.

Results. In comparing direct VAN MICs from MRSA-positive blood cultures and standard agar dilution, nearly half of the MICs from agar dilution were lower, with one sample decreasing from 1.5 to 0.75 µg ml−1. Furthermore, in seeded blood cultures, 80 % or more showed lower values from standard agar dilution compared to direct VAN MICs.

Conclusion. Our results reveal a trend towards lower MICs after positive blood culture isolates are sub-cultured. Some clinical failures among MRSA infections treated with VAN may result from this phenomenon.
Antibacterial activity and mode of action of potassium tetraborate tetrahydrate against soft-rot bacterial plant pathogens
Authors: Liu Yingyu , Filiatrault Melanie J.
Published: July 2020

Bacterial soft rot caused by the bacteria

Dickeya

and

Pectobacterium

is a destructive disease of vegetables, as well as ornamental plants. Several management options exist to help control these pathogens. Because of the limited success of these approaches, there is a need for the development of alternative methods to reduce losses. In this study, we evaluated the effect of potassium tetraborate tetrahydrate (PTB) on the growth of six

Dickeya

and

Pectobacterium

spp. Disc diffusion assays showed that

Dickeya

spp. and

Pectobacterium

spp. differ in their sensitivity to PTB. Spontaneous PTB-resistant mutants of

Pectobacterium

were identified and further investigation of the mechanism of PTB resistance was conducted by full genome sequencing. Point mutations in genes cpdB and supK were found in a single

Pectobacterium atrosepticum

PTB-resistant mutant. Additionally, point mutations in genes prfB (synonym supK) and prmC were found in two independent

Pectobacterium brasiliense

PTB-resistant mutants. prfB and prmC encode peptide chain release factor 2 and its methyltransferase, respectively. We propose the disruption of translation activity due to PTB leads to

Pectobacterium

growth inhibition. The

P. atrosepticum

PTB-resistant mutant showed altered swimming motility. Disease severity was reduced for

P. atrosepticum

-inoculated potato stems sprayed with PTB. We discuss the potential risk of selecting for bacterial resistance to this chemical.
SARS-CoV-2 sample-to-answer nucleic acid testing in a tertiary care emergency department: evaluation and utility
Authors: Jokela Pia , Jääskeläinen Anu E , Jarva Hanna , Holma Tanja , Ahava Maarit J , Mannonen Laura , Lappalainen Maija , Kurkela Satu , Loginov Raisa
Published: July 2020

Rapid sample-to-answer tests for detection of SARS-CoV-2 are emerging and data on their relative performance is urgently needed. We evaluated the analytical performance of two rapid nucleic acid tests, Cepheid Xpert® Xpress SARS-CoV-2 and Mobidiag Novodiag® Covid-19, in comparison to a combination reference of three large-scale PCR tests. Moreover, utility of the Novodiag® test in tertiary care emergency departments was assessed. In the preliminary evaluation, analysis of 90 respiratory samples resulted in 100% specificity and sensitivity for Xpert®, whereas analysis of 107 samples resulted in 93.4% sensitivity and 100% specificity for Novodiag®. Rapid SARS-CoV-2 testing with Novodiag® was made available for four tertiary care emergency departments in Helsinki, Finland between 18 and 31 May, coinciding with a rapidly declining epidemic phase. Altogether 361 respiratory specimens, together with relevant clinical data, were analyzed with Novodiag® and reference tests: 355/361 of the specimens were negative with both methods, and 1/361 was positive in Novodiag® and negative by the reference method. Of the 5 remaining specimens, two were negative with Novodiag®, but positive with the reference method with late Ct values. On average, a test result using Novodiag® was available nearly 8 hours earlier than that obtained with the large-scale PCR tests. While the performance of novel sample-to-answer PCR tests need to be carefully evaluated, they may provide timely and reliable results in detection of SARS-CoV-2 and thus facilitate patient management including effective cohorting.
An Agent Based Modeling of COVID-19: Validation, Analysis, and Recommendations
Authors: Shamil Md. Salman , Farheen Farhanaz , Ibtehaz Nabil , Khan Irtesam Mahmud , Rahman M. Sohel
Published: July 2020

The Coronavirus disease 2019 (COVID-19) has resulted in an ongoing pandemic worldwide. Countries have adopted Non-pharmaceutical Interventions (NPI) to slow down the spread. This study proposes an Agent Based Model that simulates the spread of COVID-19 among the inhabitants of a city. The Agent Based Model can be accommodated for any location by integrating parameters specific to the city. The simulation gives the number of daily confirmed cases. Considering each person as an agent susceptible to COVID-19, the model causes infected individuals to transmit the disease via various actions performed every hour. The model is validated by comparing the simulation to the real data of Ford county, Kansas, USA. Different interventions including contact tracing are applied on a scaled down version of New York city, USA and the parameters that lead to a controlled epidemic are determined. Our experiments suggest that contact tracing via smartphones with more than 60% of the population owning a smartphone combined with a city-wide lock-down results in the effective reproduction number (Rt) to fall below 1 within three weeks of intervention. In the case of 75% or more smartphone users, new infections are eliminated and the spread is contained within three months of intervention. Contact tracing accompanied with early lock-down can suppress the epidemic growth of COVID-19 completely with sufficient smartphone owners. In places where it is difficult to ensure a high percentage of smartphone ownership, tracing only emergency service providers during a lock-down can go a long way to contain the spread. No particular funding was available for this project.
Universal rules of life: Metabolic rates, biological times and the equal fitness paradigm
Authors: Burger Joseph Robert , Hou Chen , Hall Charles A.S , Brown James H.
Published: July 2020

Here we review and extend the equal fitness paradigm (EFP) as an important step in developing and testing a synthetic theory of ecology and evolution based on energy and metabolism. The EFP states that all organisms are equally fit at steady state, because they allocate the same quantity of energy, ~22.4 kJ/g/generation to production of offspring. On the one hand, the EFP may seem tautological, because equal fitness is necessary for the origin and persistence of biodiversity. On the other hand, the EFP reflects universal laws of life: how biological metabolism – the uptake, transformation and allocation of energy – links ecological and evolutionary patterns and processes across levels of organization from: i) structure and function of individual organisms, ii) life history and dynamics of populations, iii) interactions and coevolution of species in ecosystems. The physics and biology of metabolism have facilitated the evolution of millions of species with idiosyncratic anatomy, physiology, behavior and ecology but also with many shared traits and tradeoffs that reflect the single origin and universal rules of life.
Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior
Authors: Davis Gwynne L. , Minerva Adelaide R. , Lario Argentina , Rodriguez Carolyn I. , Gunaydin Lisa A.
Published: July 2020

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fastacting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine’s therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity rescued compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine’s therapeutic effects in OCD.
SimText: A text mining framework for interactive analysis and visualization of similarities among biomedical entities
Authors: Gramm Marie , Pérez-Palma Eduardo , Schumacher-Bass Sarah , Dalton Jarrod , Leu Costin , Blank-enberg Daniel , Lal Dennis
Published: July 2020

Literature exploration in PubMed on a large number of biomedical entities (e.g., genes, diseases, experiments) can be time consuming and challenging comparing many entities to one other. Here, we describe SimText, a user-friendly toolset that provides customizable and systematic workflows for the analysis of similarities among a set of entities based on words from abstracts and/or other text. SimText can be used for (i) data generation: text collection from PubMed and extraction of words with different text mining approaches, and (ii) interactive analysis of data using unsupervised learning techniques and visualization in a Shiny web application.

Availability and Implementation

We developed SimText as an open-source R software and integrated it into Galaxy, an online data analysis platform. A command line version of the toolset is available for download from GitHub athttps://github.com/mgramm1/simtext.
Changes in insulin resistance do not occur in parallel with changes in mitochondrial content and function in male rats
Authors: Genders Amanda J , Kuang Jujiao , Marin Evelyn C , Saner Nicholas J , Botella Javier , Jacques Macsue , McConell Glenn K , Andrade-Souza Victor A , Chagolla Javier , Bishop David J
Published: July 2020

Aims/hypothesis

To investigate if there is a causal relationship between changes in insulin resistance and mitochondrial respiratory function and content in rats fed a high fat diet (HFD) with or without concurrent exercise training. We hypothesised that provision of a high fat diet (HFD) would increase insulin resistance and decrease mitochondrial characteristics (content and function), and that exercise training would improve both mitochondrial characteristics and insulin resistance in rats fed a HFD.

Methods

Male Wistar rats were given either a chow diet or a high fat diet (HFD) for 12 weeks. After 4 weeks of the dietary intervention, half of the rats in each group began eight weeks of interval training.In vivoglucose and insulin tolerance was assessed, as wasex vivoglucose uptake in epitrochlearis muscle. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS).

Results

HFD rats had impaired glucose and insulin tolerance. HFD did not change CS activity in the soleus; however, it did increase CS activity in WG (Chow 5.9 ± 0.5, HFD 7.2 ± 0.7 mol h-1kg protein-1). Protein expression of components of the ETS and mitochondrial respiratory function (WG Chow 65.2 ± 8.4, HFD 88.6 ± 8.7 pmol O2 s-1mg-1) were also increased by HFD. Exercise training improved glucose and insulin tolerance in the HFD rats. Exercise training did not alter CS activity in either muscle. Mitochondrial respiratory function was increased with exercise training in the chow fed animals in soleus muscle, but not in WG. This exercise effect was absent in the HFD animals. Mitochondrial characteristics did not consistently correlate with insulin or glucose tolerance.

Conclusions/interpretation

HFD induced insulin resistance, but it did not negatively affect any of the measured mitochondrial characteristics. Exercise training improved insulin resistance, but without changes in mitochondrial respiration and content. The lack of an association between mitochondrial characteristics and insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that defects in mitochondrial respiration and content are not responsible for insulin resistance in HFD rats.
EnterococcalPrgU mitigates PrgB overexpression toxicity by binding to intergenic RNA downstream of the PQpromoter
Authors: Lassinantti Lena , Camacho Martha I , Erickson Rebecca J B , Willett Julia L E , De Lay Nicholas R. , ter Beek Josy , Dunny Gary M , Christie Peter J , Berntsson Ronnie P-A
Published: July 2020

Efficient horizontal gene transfer of the conjugative plasmid pCF10 fromEnterococcus faecalisdepends on the sex pheromone cCF10, which induces the expression of the Type 4 Secretion System (T4SS) genes controlled by the PQpromoter. The pheromone responsive PQpromoter is strictly regulated to prevent overproduction of theprgQoperon, which contains the T4SS, and to limit the cell toxicity caused by overproduction of PrgB, a T4SS adhesin involved in cellular aggregation. PrgU plays an important role in regulating this toxicity by decreasing PrgB production. PrgU has an RNA-binding fold, prompting us to test whether PrgU exerts its regulatory control through binding ofprgQtranscripts. With a combination oflacZreporter fusion, northern blot, and RNAseq analyses, we provide evidence that PrgU binds a specific RNA sequence within the intergenic region (IGR), ca 400 bp downstream of the PQpromoter. PrgU-IGR binding reduces levels of downstream transcripts, with the strongest decrease seen forprgBmessages. Consistent with these findings, we determined that pCF10-carrying cells expressingprgUdecreased transcript levels more rapidly than isogenic cells deleted ofprgU. Finally, purified PrgU bound RNAin vitro, but without sequence specificity, suggesting that PrgU requires a specific RNA structure or one or more host factors to bind its RNA targetin vivo. Together, our results support a working model where PrgU binding to the IGR serves to recruit RNase(s) for targeted degradation of downstream transcripts.

Importance

Bacteria utilize Type 4 Secretion Systems (T4SS) to efficiently transfer DNA from donor to recipient cells, thereby spreading genes encoding for antibiotic resistance as well as various virulence factors. The conjugative plasmid pCF10 fromEnterococcus faecalis, originally isolated from clinical isolates, serves as a model system for these processes in Gram-positive bacteria. It is very important to strictly regulate the expression of the T4SS proteins for the bacteria, as some of these proteins are highly toxic to the cell. Here, we identify the mechanism by which PrgU performs its delicate fine tuning of the expression levels. AsprgUgenes are present in various conjugative plasmids and transposons, this provides an important new insight into the bacterial repertoire of regulation mechanisms of these clinically important systems.
Correlation of ELISA based with random access serologic immunoassays for identifying adaptive immune response to SARS-CoV-2
Authors: Nguyen Nguyen N. , Mutnal Manohar B. , Gomez Richard R. , Pham Huy N. , Nguyen Lam T. , Koss William , Rao Arundhati , Arroliga Alejandro C. , Wang Liping , Wang Dapeng , Hua Yinan , Powell Priscilla R. , Chen Li , McCormack Colin C. , Linz Walter J. , Mohammad Amin A.
Published: July 2020

Public health emergency of SARS-CoV-2 has facilitated diagnostic testing as a related medical countermeasure against COVID-19 outbreak. Numerous serologic antibody tests have become available through an expedited federal emergency use only process. This paper highlights the analytical characteristic of an ELISA based assay by AnshLabs and three random access immunoassay (RAIA) by DiaSorin, Roche, and Abbott that have been approved for emergency use authorization (EUA), at a tertiary academic center in a low disease-prevalence area. The AnshLabs gave higher estimates of sero-prevalence, over the three RAIA methods. For positive results, AnshLabs had 93.3% and 100% concordance with DiaSorin or Abbott and Roche respectively. For negative results, AnshLabs had 69.7% and 73.0% concordance with DiaSorin and Roche or Abbott respectively. All discrepant samples that were positive by AnshLabs and negative by RAIA tested positive by all-in-one step SARS-CoV-2 Total (COV2T) assay performed on the automated Siemens Advia Centaur XPT analyzer. None of these methods, however, are useful in early diagnosis of SARS-CoV-2.
Forcing Seasonality of influenza-like epidemics with daily Solar resonance
Authors: Nicastro Fabrizio , Sironi Giorgia , Antonello Elio , Bianco Andrea , Biasin Mara , Brucato John R. , Ermolli Ilaria , Pareschi Giovanni , Salvati Marta , Tozzi Paolo , Trabattoni Daria , Clerici Mario
Published: July 2020

Seasonality of acute viral respiratory diseases is a well-known and yet not fully understood phenomenon. Several models have been proposed to explain the regularity of yearly recurring outbreaks and the phase-differences observed at different latitudes on Earth. Such models take into account known internal causes, primarily the periodic emergence of new virus variants that evade the host immune response. Yet, this alone, is generally unable to explain the regularity of recurrences and the observed phase-differences.

Here we show that seasonality of viral respiratory diseases, as well as its distribution with latitude on Earth, can be fully explained by the virucidal properties of UV-B and A Solar photons through a daily, minute-scale, resonant forcing mechanism. Such an induced periodicity can last, virtually unperturbed, from tens to hundreds of cycles, and even in presence of internal dynamics (host’s loss of immunity) much slower than seasonal will, on a long period, generate seasonal oscillations.
The benefits of peer transparency in safe workplace operation post pandemic lockdown
Authors: Wey Arkady , Champneys Alan , Dyson Rosemary J. , Alwan Nisreen A. , Barker Mary
Published: July 2020

The benefits, both in terms of productivity and public health, are investigated for different levels of engagement with the test, trace and isolate procedures in the context of a pandemic in which there is little or no herd immunity. Simple mathematical modelling is used in the context of a single, relatively closed workplace such as a factory or back-office where, in normal operation, each worker has lengthy interactions with a fixed set of colleagues.

A discrete-time SEIR model on a fixed interaction graph is simulated with parameters that are motivated by the recent COVID-19 pandemic in the UK during a post-peak phase, including a small risk of viral infection from outside the working environment. Two kinds of worker are assumed,transparentswho regularly test, share their results with colleagues and isolate as soon as a contact tests positive for the disease, andopaqueswho do none of these. Moreover, the simulations are constructed as a “playable model” in which the transparency level, disease parameters and mean interaction degree can be varied by the user. The model is analysed in the continuum limit.

All simulations point to the double benefit of transparency in maximising productivity and minimising overall infection rates. Based on these findings, public policy implications are discussed on how to incentivise this mutually beneficial behaviour in different kinds of workplace, and simple recommendations are made.