bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a field-friendly faeces drying and storage method for quantifying faecal glucocorticoid metabolites in African elephants (Loxodonta africana) opens up new perspectives for conservationists
Authors: Lacomme Laura , Guerbois Chloé , Fritz Hervé , Ganswindt André , Rey Benjamin
Published: August 2023

Faecal glucocorticoid metabolites (fGCMs) are a relevant means of non-invasively assessing adrenocortical activity and thus, a key physiological stress response in wildlife populations. However, the widespread use of fGCMs as a stress-related biomarker in conservation biology is often hampered by the logistical challenge of storing collected faecal material frozen until it reaches the laboratory for analysis. Although alternative approaches to minimize potential alteration of fGCM composition post-defecation have been recently identified, there is to our knowledge, no satisfactory alternative method established for the preservation of elephant dung. In this study, we validated a field-friendly protocol for dehydrating African elephant faeces samples using a food dehydrator with desiccant and investigated the stability of fGCM concentrations in the dehydrated faeces when stored at ambient temperature. We collected 40 faecal samples from African elephants and compared fGCM concentrations of freeze-dried and dehydrated sample sub-sets. Samples dried in the field showed a slight but significant overall −6% reduction in fGCM concentration compared with frozen control samples. However, fGCM concentrations following field dehydration protocol match those of control samples with high accuracy, as evidenced by the low bias and strong coefficient of determination between the two approaches (R2 = 0.88). In addition, over nearly 2 months, storage time at ambient temperature of the dehydrated samples had no effect on the fGCM concentrations compared with those measured in the control samples (F-statistic = 1.82; P = 0.18). Dehydrating the samples in the field thus provides an easy and cost-effective alternative to freezing, especially when working in remote areas with unstable electrical supply. Our results encourage the widespread use of fGCMs by conservationists as non-invasive means of steroid monitoring of African elephants in the current context of a general increase in wildlife welfare research. Future studies are needed to extend the use of this protocol to other species and to other steroid classes.
From Intent to Impact: Building University-Assisted Community Schools in New Mexico
Authors: Gherardi Stacy A , Greenberg David
Published: August 2023

Universities have the potential to bring significant assets to community school development, and community school models align with emerging priorities in higher education, including shifts toward community engagement. University-assisted community schools (UACS) present an ideal place for these mutual interests to be met, although barriers to these partnerships exist. Experiences from the state of New Mexico provide a unique case study of successes and challenges with the development of UACS. This article draws on the historic and current efforts to build UACS in New Mexico, sharing key considerations for university faculty, PK–12 educators and administrators, social workers, and social work faculty. The authors integrate literature around the development of UACS and their personal experiences as university faculty and district/community leaders in New Mexico, describing successful partnerships and barriers to sustainability. These experiences are used to propose key features, structures, and resources to consider in the development of UACS and the integration of social work into these structures.
Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication
Authors: Sá Sales Leonardo Adolpho , Pinheiro Fernando Antônio Siqueira , Pinto João Odilo Gonçalves , Santos Armênio Aguiar , Souza Miguel Ângelo Nobre
Published: August 2023

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7 years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6 months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1 mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7 mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.
The Diagnostic Utility of Volatile Organic Compounds in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Krishnamoorthy Ashwin , Chandrapalan Subashini , Ahmed Marriam , Arasaradnam Ramesh P
Published: August 2023

Background

Volatile organic compounds [VOCs] show promise as potential biomarkers of for ulcerative colitis and Crohn’s disease, two chronic, idiopathic, gastrointestinal disorders with diagnostic and management challenges. Non-invasive biomarkers aid early diagnosis and management. In this study we review studies of diagnostic accuracy of VOCs in inflammatory bowel disease.

Methods

A systematic search was carried out on the Pubmed and Scopus databases; with 16 studies reviewed and meta-analysis carried out on 10.

Results

Meta-analysis of 696 inflammatory bowel disease [IBD] cases against 605 controls revealed a pooled sensitivity and specificity of 87% (95% confidence interval [CI], 0.79 - 0.92) and 83% [95% CI, 0.73 - 0.90], respectively. Area under the curve [AUC] was 0.92.

Conclusion

VOCs perform very well as non-invasive biomarkers of IBD, with much scope for future improvement and research.
The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors: Melin Johanna , Forslund Maria , Alesi Simon , Piltonen Terhi , Romualdi Daniela , Spritzer Poli Mara , Tay Chau Thien , Pena Alexia , Witchel Selma Feldman , Mousa Aya , Teede Helena
Published: August 2023

Objective

Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps remain regarding its efficacy and the specific outcomes in this population. This review evaluates the effectiveness of metformin and lifestyle modification compared with placebo in the management of PCOS and will inform the forthcoming, 2023 evidence-based PCOS guidelines.

Design

Systematic review and meta-analysis of the literature.

Methods

A search was performed in MEDLINE, EMBASE, PsycINFO, All EBM, and CINAHL. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomized controlled trials published in English through July 2022.

Results

Moderate certainty of evidence showed a larger reduction of body mass index (BMI) (mean difference [MD] −0.53, 95% confidence interval [CI] −0.95 to −0.12 kg/m2), homeostatic model assessment for insulin resistance (MD −0.50, 95% CI −0.91 to −0.09) (critical outcomes), and fasting glucose (MD −0.13, 95% CI −0.19 to −0.07 mmol/L) with metformin compared to placebo with increased mild gastrointestinal adverse effects (odds ratio [OR] 7.67, 95% CI 2.74–21.46). Low certainty of evidence showed a larger reduction of waist–hip ratio (MD −0.02, 95% CI −0.03 to −0.00), total cholesterol (MD −0.24, 95% CI −0.43 to −0.05 mmol/L), low-density lipoprotein (MD −0.16, 95% CI −0.30 to −0.01 mmol/L), and triglycerides (MD −0.11, 95% CI −0.20 to −0.02 mmol/L) with metformin than placebo.

Conclusions

Metformin should be considered an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance, and lipids.
Diversity and characterization of antagonistic bacteria against Pseudomonas syringae pv. actinidiae isolated from kiwifruit rhizosphere
Authors: Yan Zhewei , Fu Min , Mir Sajad Hussain , Zhang Lixin
Published: August 2023

Kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) is a severe global disease. However, effective biological control agents for controlling Psa are currently unavailable. This study aimed to screen potential biological control agents against Psa from the kiwifruit rhizosphere. In this study, a total of 722 isolates of bacteria were isolated from the rhizosphere of kiwifruit orchards in five regions of China. A total of 82 strains of rhizosphere bacteria showed antagonistic effects against Psa on plates. Based on amplified ribosomal DNA restriction analysis (ARDRA), these antagonistic rhizosphere bacteria were grouped into 17 clusters. BLAST analyses based on 16S rRNA gene sequence revealed 95.44%–100% sequence identity to recognized species. The isolated strains belonged to genus Acinetobacter, Bacillus, Chryseobacterium, Flavobacterium, Glutamicibacter, Lysinibacillus, Lysobacter, Pseudomonas, Pseudarthrobacter, and Streptomyces, respectively. A total of four representative strains were selected to determine their extracellular metabolites and cell-free supernatant activity against Psa in vitro. They all produce protease and none of them produce glucanase. One strain of Pseudomonas sp. produces siderophore. Strains of Bacillus spp. and Flavobacteria sp. produce cellulase, and Flavobacteria sp. also produce chitinase. Our results suggested that the kiwifruit rhizosphere soils contain a variety of antagonistic bacteria that effectively inhibit the growth of Psa.
VExD: a curated resource for human gene expression alterations following viral infection
Authors: Dexheimer Phillip J , Pujato Mario , Roskin Krishna M , Weirauch Matthew T
Published: August 2023

Much of the host antiviral response is mediated through changes to host gene expression levels. Likewise, viruses induce changes to host gene expression levels in order to promote the viral life cycle and evade the host immune system. However, there is no resource that specifically collects human gene expression levels pre- and post-virus infection. Further, public gene expression repositories do not contain enough specialized metadata to easily find relevant experiments. Here, we present the Virus Expression Database (VExD), a freely available website and database, that collects human gene expression datasets in response to viral infection. VExD contains ∼8,000 uniformly processed samples obtained from 289 studies examining 51 distinct human viruses. We show that the VExD processing pipeline captures known antiviral responses in the form of interferon-stimulated genes. We further show that the datasets collected in VExD can be used to quickly identify supporting data for experiments performed in human cells or model organisms. VExD is freely available at https://vexd.cchmc.org/.
Structural Network Efficiency Predicts Conversion to Incident Parkinsonism in Patients With Cerebral Small Vessel Disease
Authors: Cai Mengfei , Jacob Mina A , Marques José , Norris David G , Duering Marco , Esselink Rianne A J , Zhang Yuhu , de Leeuw Frank-Erik , Tuladhar Anil M
Published: August 2023

Background

To investigate whether structural network disconnectivity is associated with parkinsonian signs and their progression, as well as with an increased risk of incident parkinsonism.

Methods

In a prospective cohort (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study) consisting of 293 participants with small vessel disease (SVD), we assessed parkinsonian signs and incident parkinsonism over an 8-year follow-up. In addition, we reconstructed the white matter network followed by graph-theoretical analyses to compute the network metrics. Conventional magnetic resonance imaging markers for SVD were assessed.

Results

We included 293 patients free of parkinsonism at baseline (2011), with a mean age 68.8 (standard deviation [SD] 8.4) years, and 130 (44.4%) were men. Nineteen participants (6.5%) developed parkinsonism during a median (SD) follow-up time of 8.3 years. Compared with participants without parkinsonism, those with all-cause parkinsonism had higher Unified Parkinson’s Disease Rating scale (UPDRS) scores and lower global efficiency at baseline. Baseline global efficiency was associated with UPDRS motor scores in 2011 (β = −0.047, p < .001) and 2015 (β = −0.84, p < .001), as well as with the changes in UPDRS scores during the 4-year follow-up (β = −0.63, p = .004). In addition, at the regional level, we identified an inter-hemispheric disconnected network associated with an increased UPDRS motor score. Besides, lower global efficiency was associated with an increased risk of all-cause and vascular parkinsonism independent of SVD markers.

Conclusions

Our findings suggest that global network efficiency is associated with a gradual decline in motor performance, ultimately leading to incident parkinsonism in the elderly with SVD. Global network efficiency may have the added value to serve as a useful marker to capture changes in motor signs.
Potential Association of Neutrophil Extracellular Traps With Cognitive Impairment in Cerebral Small Vessel Disease
Authors: Shi Yachen , Mao Haixia , Miao Weifeng , Deng Jingyu , Gao Qianqian , Zeng Siyuan , Ma Lin , Han Yan , Ji Wei , Li Ying , Xi Guangjun , You Yiping , Chen Kefei , Shao Junfei , Mao Xuqiang , Fang Xiangming , Wang Feng
Published: August 2023

No acceptable biomarker can facilitate the early identification of cognitive impairment associated with cerebral small vessel disease (CSVD) in the older persons. The neutrophil extracellular traps (NETs) in the inflammation response of circulatory and central systems are essential in destroying the blood–brain barrier. The present study aims to explore the potential associations of plasma NETs with cognitive performance in CSVD. We recruited 146 CSVD patients and 66 healthy controls (HCs), and comprehensive neuropsychological assessments and multimodal magnetic resonance imaging were conducted. Three NETs markers, namely citrullination of histone H3, neutrophil elastase–DNA, and myeloperoxidase (MPO)–DNA, and 4 oxidative stress-related indexes in plasma samples, were measured. The plasma levels of 3 NETs markers were more significantly elevated in CSVD patients than in HCs. Significant correlations of the 3 NETs markers were observed with multiple cognitive domain scores. Furthermore, higher plasma malondialdehyde and NETs levels were significantly associated with the worse Montreal Cognitive Assessment scores among CSVD patients. Moreover, plasma MPO–DNA levels significantly mediated the effect of the amplitude of low-frequency fluctuation value within the bilateral caudate and the scores of global cognitive function, executive function, and information processing speed. Additionally, a panel of 3 NETs markers had the highest area under the curve value to distinguish the cognitively impaired CSVD patients from HCs and nonimpaired ones. Therefore, plasma NETs may be potential biomarkers for early diagnosis of CSVD-related cognitive impairment. Activated lipid peroxidation in circulation and impaired caudate function support potential associations of plasma NETs in cognitively impaired CSVD patients.
Lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) lncRNA differentially regulates gene and protein expression, signaling and morphology of human ocular cells
Authors: Schmitt Heather M , Hake Kristyn M , Perkumas Kristin M , Lê Brandon M , Suarez Maria F , De Ieso Michael L , Rahman Rashad S , Johnson William M , Gomez-Caraballo María , Ashley-Koch Allison E , Hauser Michael A , Stamer W Daniel
Published: August 2023

Pseudoexfoliation glaucoma (PEXG) is characterized by dysregulated extracellular matrix (ECM) homeostasis that disrupts conventional outflow function and increases intraocular pressure (IOP). Prolonged IOP elevation results in optic nerve head damage and vision loss. Uniquely, PEXG is a form of open angle glaucoma that has variable penetrance, is difficult to treat and does not respond well to common IOP-lowering pharmaceuticals. Therefore, understanding modulators of disease severity will aid in targeted therapies for PEXG. Genome-wide association studies have identified polymorphisms in the long non-coding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) as a risk factor for PEXG. Risk alleles, oxidative stress and mechanical stretch all alter LOXL1-AS1 expression. As a long non-coding RNA, LOXL1-AS1 binds hnRNPL and regulates global gene expression. In this study, we focus on the role of LOXL1-AS1 in the ocular cells (trabecular meshwork and Schlemm’s canal) that regulate IOP. We show that selective knockdown of LOXL1-AS1 leads to cell-type-specific changes in gene expression, ECM homeostasis, signaling and morphology. These results implicate LOXL1-AS1 as a modulator of cellular homeostasis, altering cell contractility and ECM turnover, both of which are well-known contributors to PEXG. These findings support LOXL1-AS1 as a key target for modifying the disease.
Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study
Authors: Kogan Cary S , Garcia-Pacheco José A , Rebello Tahilia J , Montoya Madeline I , Robles Rebeca , Khoury Brigitte , Kulygina Maya , Matsumoto Chihiro , Huang Jingjing , Medina-Mora María Elena , Gureje Oye , Stein Dan J , Sharan Pratap , Gaebel Wolfgang , Kanba Shigenobu , Andrews Howard F , Roberts Michael C , Pike Kathleen M , Zhao Min , Ayuso-Mateos José Luis , Sadowska Karolina , Maré Karen , Denny Keith , Reed Geoffrey M
Published: August 2023

Background

Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services.

Method

A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization’s Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms.

Results

On average, respondents’ well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time.

Conclusions

This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic.
Analysis of point-contact models of the bounce of a hard spinning ball on a compliant frictional surface
Authors: Biber Stanisław W , Champneys Alan R , Szalai Robert
Published: August 2023

Inspired by the turf–ball interaction in golf, this paper seeks to understand the bounce of a ball that can be modelled as a rigid sphere and the surface as supplying a viscoelastic contact force in addition to Coulomb friction. A general formulation is proposed that models the finite time interval of bounce from touch-down to lift-off. Key to the analysis is understanding transitions between slip and roll during the bounce. Starting from the rigid-body limit with an energetic or Poisson coefficient of restitution, it is shown that slip reversal during the contact phase cannot be captured in this case, which generalizes to the case of pure normal compliance. Yet, the introduction of linear tangential stiffness and damping does enable slip reversal. This result is extended to general weakly nonlinear normal and tangential compliance. An analysis using the Filippov theory of piecewise-smooth systems leads to an argument in a natural limit that lift-off while rolling is non-generic and that almost all trajectories that lift off do so under slip conditions. Moreover, there is a codimension-one surface in the space of incoming velocity and spin which divides balls that lift off with backspin from those that lift off with topspin. The results are compared with recent experimental measurements on golf ball bounce and the theory is shown to capture the main features of the data.
Correction to: d-elliptic Loci in Genus 2 and 3
Authors: Lian Carl
Published: August 2023

We consider the loci of curves of genus 2 and 3 admitting a $d$-to-1 map to a genus 1 curve. After compactifying these loci via admissible covers, we obtain formulas for their Chow classes, recovering results of Faber–Pagani and van Zelm when $d=2$. The answers exhibit quasimodularity properties similar to those in the Gromov–Witten theory of a fixed genus 1 curve; we conjecture that the quasimodularity persists in higher genus and indicate a number of possible variants.
Phylogeography and species delimitation of the Asian cavity-nesting honeybees
Authors: Su Yong-Chao , Chiu Yi-Fan , Warrit Natapot , Otis Gard W , Smith Deborah Roan
Published: August 2023

We examine phylogenetic relationships among species and populations of Asian cavity-nesting honeybees, emphasizing detection of potential unrecognized species in the geographically widespread Apis cerana Fabricius (Hymenoptera, Apidae). We carried out a phylogenetic analysis of genome-wide single nucleotide polymorphisms (SNPs) using BEASTv1.8.4 and IQ-TREE 2. Our samples cover the largest geographic area and number of populations of Asian cavity-nesting honey bees sampled to date. We used STRUCTURE, Bayes Factor Delimitation, and discriminant analysis of principal components to infer probable species among populations of cavity-nesting honeybees currently recognized as Apis cerana. Our results support 4 species within A. cerana: the yellow “plains” honeybee of India and Sri Lanka; the lineage inhabiting the oceanic Philippine islands; the Sundaland lineage found in Indonesia, Malaysia, and parts of southeast Asia; and a Mainland lineage, which we provisionally consider A. cerana in a narrow sense.
P08 Preventing and managing urinary tract infections: using thematic analysis to explore interventions and strategies implemented by NHS commissioning organizations in English primary care, 2017–22
Authors: Sides Eirwen , Lecky Donna , Taborn Esther , O’Neill Luke , Cooper Emily
Published: August 2023

Objectives

To identify and explore strategies, interventions and activities used by English Clinical Commissioning Groups (CCGs) to improve prevention and management of urinary tract infections (UTIs) from 2017–22.

Methods

Online questionnaires were sent to primary care chief nurses and medicines optimization leads via regional infection prevention control (IPC) and antimicrobial stewardship (AMS) leads August–September 2022. Qualitative data were mapped to the Theoretical Domains Framework.

Results

Response rate was 14.1% (56/397 participants approached), with representation from 29.2% (31/106) English CCGs. Respondents provided 201 examples of UTI interventions. Themes identified included: (i) populations and settings; (ii) aspects of UTI targeted; (iii) types and functions of interventions and activities; (iv) resources, tools and policies; and (v) implementation strategies. Education and training were the most used type of intervention, while changing the environment to facilitate ideal behaviours was the least used intervention type. Most interventions targeted general practice staff and patients accessing primary care, followed by care home staff and residents and their families. The most used success measures included reduction in antibiotic prescribing (54.5%, 97/178 intervention examples); positive feedback from stakeholders (42.1%, 75/178); and increased adherence to national diagnostic guidelines (32.6%, 58/178). However, 48.8% (20/41) stated their team’s UTI activities had not been evaluated, indicating that success was determined using informal data or perceived outcomes. Barriers to implementation of UTI interventions included: lack of resources and time; low staff engagement, inaccurate data due to lack of clinical coding; inconsistent systems and processes; and lack of dedicated roles. Facilitators to implementation included: availability of tools; financial incentives; multidisciplinary collaboration; sharing of information; staff motivation; embedding resources into systems; digitalization; and dedicated roles.

Conclusions

Multidisciplinary teams and cross-sector collaboration are key facilitators for implementation of UTI interventions. Although some teams are already using robust success measures, there is a need to improve how interventions are evaluated to inform resource allocation and planning. Education and training interventions should address or leverage the barriers and facilitators identified, including clinical coding skills, embedding resources and tools into existing systems and auditing adherence to diagnostic and antibiotic prescribing guidance. There may be missed opportunities for intervention types that are less widely used e.g. changing environmental factors.
P10 Ceftazidime/avibactam for OXA-48 urinary tract infections—a 12 month remissive study
Authors: Fernandes Afonso Paes , Silva Beatriz , Coutinho Ana
Published: August 2023

Background

Ceftazidime/avibactam is a novel antibiotic for MDR bacterial infections. Despite its high cost, from 1 January 2022 to 31 December 2022, 23 patients out of 230 hospital beds at the Hospital of Cascais received it. Seven of these patients had OXA-48-producing urinary tract infections (UTIs). One was a post-stroke ICU patient with a urinary catheter; all others were in the urology unit, with no invasive devices.

Objectives

To assess appropriateness, efficacy and renal toxicity of ceftazidime 2000 mg + avibactam 500 mg in the seven UTI patients with isolation of OXA-48-producing bacteria in urine samples.

Methods

From patient history, lab analysis and drug chart we assessed appropriateness—by meropenem (alternative therapy if MIC <16.000 mg/L); efficacy—from overall outcomes; renal toxicity—by evaluating serum creatinine progression (the rationale being SPC describes increases in serum creatinine as a frequent adverse reaction). We also describe dose and days of therapy.

Results

All had antibiotic adequacy, two meropenem MICs <16.000 mg/L were found but carbapenem therapy was not recommended due to drug interaction or allergy. Median days of therapy was 8.7 days. Four outcomes were successful, the ICU patient had a death not related to infection, one urology unit patient died and in one patient treatment was not successful—OXA-48 was still detected in urine samples after 7 days of therapy. No renal toxicity from ceftazidime/avibactam was noted.

Conclusions

Ceftazidime/avibactam prescription in UTIs has been adequate, safe and efficient in some patients. Literature describes that efficacy of ceftazidime/avibactam varies with kidney status. Kinetics is known to be linear, so therapeutic drug monitoring will be the way forward. Further study will be necessary to address definitive safety and efficiency.
P12 Assessing the clinical utility of antibiotics for urinary tract infections in India: findings from a questionnaire survey
Authors: Gupta Narmada Prasad , Chibber Percy , Oza Umesh , Kumar Anant , Ramesh D , Pandey Sanjay , Mallikarjuna Reddy N , Kundu Bibash , Taneja Rajesh , Kamath Ganesh
Published: August 2023

Background

We aimed to formulate a consensus for the therapeutic utilization of antibiotics based on contemporary evidence and the real-world experiences of the clinicians at the forefront of the care of patients with urinary tract infection (UTI).

Methods

We developed customized technological response system for mapping exercise and panel of eminent specialists was convened. Prior consent was obtained, and the weblink of the questionnaire was provided. Sub-expert nationwide panel (n=397), across India (PRISM Survey group), rated their level of agreement with 11 questions with each item on a five-point Likert scale and 5 objective response questions. The consensus was pre-defined if the weighted mean score for the Likert scale was >100. Data were statistically analysed by GraphPad software version 9.5.0.

Results

The mean years of experience were 9.2 years (SD ±10, 95% CI 8.2–10), and cumulative clinical experience was 3669 person-years. The predominant clinical practice setting of the respondents was a public hospital (58.6%). The highest agreement score in the decreasing rank order (of adjusted weighted mean score) for UTI were: antibiotic resistance is a major challenge (126.1), oral fosfomycin-based regimens are effective against MDR pathogens (123.4), is a good option for bacterial biofilm reduction (121.7), the potential to manage recurrent lower UTI (121.6), oral fosfomycin along with nitrofurantoin is been useful to manage MDR UTI (106.8), nitrofurantoin and fosfomycin are chosen as empirical treatment (103.7), fosfomycin has stood the test of time (120.2). Adjusted mean response scores (±SD, 95% CI) for consensus were: agree (73±9.4, 95% CI 66 to 79) followed by strongly agree (32±13, 95% CI 24 to 41), neither agree nor disagree (13±4.9, 95% CI 9.8 to 16), disagree (−6.5±4.7, 95% CI −9.7 to −3.4), strongly disagree (−0.86±0.9, 95% CI −1.5 to −0.26).

Conclusions

In the era of MDR UTI, time-tested oral fosfomycin and nitrofurantoin can improve management of UTI without increasing the complexity.
P13 Predictive value of urinalysis and urine culture in bacteraemic adults without localizing urinary features: a retrospective cohort study
Authors: Hopkins Chris , Beaumont Jenna , Young Nicholas
Published: August 2023

Background

Urinalysis (UA) and urine culture (UC) are commonly used in patients with bacteraemia to diagnose a urinary focus of infection. The predictive value of these investigations in patients without localizing urinary features is uncertain. We hypothesized that UA/UC would have extremely low predictive value in patients with bacteraemia and neither localizing urinary features nor risk factors for bacteraemic UTI (bUTI).

Methods

This was a retrospective cohort study of hospitalized adults with community-onset bacteraemia in 2019 at Middlemore Hospital (Auckland, New Zealand). The suspected focus of infection at first assessment was determined by reviewing clinical notes from the initial presentation using the admitting clinician’s preferred diagnosis plus at least one supportive clinical feature. The final diagnosis of focus of bacteraemia (bUTI versus non-urinary) was determined by investigators based on blood and urine culture concordance, with supportive clinical, laboratory or imaging features. Defined localizing urinary features were determined by investigators from notes. Positive and negative predictive value of UA/UC for diagnosing bUTI was calculated among those with initially unclear or non-urinary focus of infection. Univariate analysis was performed for patients with initially unclear focus of infection, for risk factors associated with final diagnosis of bUTI.

Results

In total, 871 patients were included. The admitting clinician’s suspected focus was urinary in 219, unclear in 304 and non-urinary in 348. A final diagnosis of bUTI was found in 342 (39.3%), of whom 110 (32.2%) lacked any localizing urinary features. After excluding localizing urinary features, bUTI was diagnosed in 98/243 (40.3%) with initially unclear focus and 12/326 (3.7%) with suspected non-urinary focus. UA/UC PPV was 5.2%/25%, respectively, when initial focus was non-urinary, but 51.5%/75% when initial focus was unclear. Amongst patients with initially unclear focus, risk factors for bUTI included age >75, urinary catheter/nephrostomy, invasive urologic procedure within 3 months and cognitive impairment. However, of those with bUTI, 22/98 (22.4%) had none of these risk factors.

Conclusions

bUTI occurs in a significant minority of bacteraemic patients where initial focus is unclear and where localizing urinary features are absent, including in patients without associated risk factors. UA/UC is a reasonable investigation in bacteraemia of uncertain focus, but results should be interpreted cautiously. UA has excellent NPV but very poor PPV. Among patients with bacteraemia, initially suspected non-urinary focus of infection, and without localizing urinary features, UA/UC can be safely withheld and bUTI is very uncommon. A prospective study using initial clinical criteria would provide more relevant predictive values for clinicians.
P16 COVID-19 and urinary tract infection: the main manifestations and their management
Authors: Chichirelo-Konstantynovych Kiarina , Konstantynovych Tetyana
Published: August 2023

Background

Despite the predominant injury from COVID-19 being to the respiratory system, there are presently several reports of urinary symptoms. The majority of them are due to comorbid urinary tract infection (UTI) but separate clinical signs can be related to the COVID-19 origin.

Objectives

To investigate the frequency of UTI symptoms among patients recovering from COVID-19.

Subjects and Methods

A total of 150 patients (males, 49.3%; average age 57 years old) at the average period of recovering after COVID-19 (6–7 months) were asked about quality, frequency and severity of the main UTI symptoms and antibiotics prescription for their treatment.

Results

Sixty-one (40.7%) of the individuals asked reported anamnestic UTI (nephritis, glomerulonephritis, urolithiasis) prior to COVID-19 infection. One hundred and nine (72.6%) patients mentioned the appearance of UTI symptoms after recovering from COVID-19 (50% of them observed complaints in the period 3–4 months after hospital discharge). The prevalence of urinary symptoms looked as follows: haematuria, 17.43%; nocturia, 27.25%; incomplete emptying, 19.27%; frequent urination, 11.93%; leukocyturia, 24.12%. Forty-four patients (40.36%) visited family doctors for consultation regarding urinary complaints. Thirty-seven patients (33.94%) were recommended antibiotic therapy according to UTI diagnosis.

Conclusions

Lower urinary tract symptoms are highly prevalent among COVID-19 patients. A possible reason is ACE-2, an essential receptor for the SARS-CoV-2 spike protein. COVID-19 can worsen previous chronic urinary tract pathologies and increase the risk of new infection, thereby creating the need for additional antibiotics.
P20 Rapid 15 min test to identify the three most common Gram-negative uropathogens in urinary tract infections
Authors: Rama Sylvain , Kyriakides Mathew , Newman Henry , Bonney-Bhandal Kabir , Preece James , Vendeville Jean-Baptiste , Dorh Neciah , Dorh Josephine
Published: August 2023

Background

Every year, 6.2 million cases of urinary tract infection (UTI) are reported in England and Wales and have the second highest antibiotic prescription rate. The absence of fast and sensitive diagnostic tests has increased empirical antibiotic use and has contributed to the rise of antibiotic-resistant infections. To address this challenge, we have developed NANOPLEX™: a rapid 15 min test that uses glycan-functionalized-latex nanoparticles, microscopy and image-analysis software to identify and enumerate samples with bacteria. In this work, we show that NANOPLEX™ can correctly identify the three most common uropathogens using lab reference strains, clinical isolates and clinical urine samples.

Materials and Methods

The NANOPLEX™ assay was performed as per Vendeville et al. 2021.1 ACS Biomater 2022; 8, 1:242-252. Clinical isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were obtained from an NHS clinical microbiology lab waste stream. N=30 isolates (per species) were tested via single-blind study protocols at concentrations of 10³–108 cfu/mL and compared with microbial culture to define performance metrics (sensitivity, specificity, PPV, NPV and accuracy) of each probe.

Results

A total of 90 isolates were tested against their target probes and demonstrated >90% accuracy (sensitivity 88%–90%, specificity 94%–98%, PPV 93%–98%, NPV 88%–90%, accuracy 91%–94%) for all probe-bacteria combinations at clinically significant concentrations (105 cfu/mL).

Conclusions

NANOPLEX™ was able to successfully detect the top three common Gram-negative pathogens in UTI at clinically relevant concentrations. A compact hardware and single-use cartridge system is under development to enable urologists to conduct rapid and accurate UTI testing in point-of-care environments. Larger clinical studies are planned to clinically validate these results.
P24 Point of care rapid urinary tract infection phenotypic antibiotic susceptibility test
Authors: Roegner Megan , Butler Megan , Millirons Paula
Published: August 2023

Background

Urinary tract infections (UTIs) are one of the most common infections in the world today. In the last few years, the occurrence of antimicrobial resistant pathogens causing UTIs has rapidly increased. One in three UTIs are trimethoprim/sulfamethoxazole (Bactrim) resistant, and one in five are resistant to other common antibiotic choices. This growing resistance is mainly due to overuse or misuse of antibiotics. The strongest tool the medical community has available to combat antimicrobial resistance (AMR) is rapid, correct application of antibiotics to an identified bacterial infection. Clinics and physician offices seek on-site rapid solutions to speed the pathway to timely and appropriate antibiotic therapies. GeneCapture is developing products that perform rapid UTI pathogen identification and antimicrobial susceptibility tests (ASTs) directly from infected urine samples. The AST provides a susceptible versus non-susceptible call in under 2 h and can be applied to samples with single or mixed pathogens. A portable tabletop instrument and disposable cartridge are being engineered to run this test at the point of care, allowing same-day prescriptions. The process is currently operational on the lab bench.

Methods

Fluorescent labelling of bacterial species, followed by optical counting, determines population growth with/without a suite of antibiotics. An on-board algorithm instantly converts raw cell numbers into a differential call of susceptible or non-susceptible for each bug/drug pair. A disposable cartridge with on-board antibiotics has been designed and is being finalized for fabrication. The optical counting is operating in a desktop device.

Results

Testing to date includes 124 strains from 7 of the most common UTI and wound pathogens against a panel of six antibiotics. A total of 541 antibiotic/bacterial strain pairs in single or multiple pathogen antibiotic susceptibility testing produce an initial 88.7% agreement to gold standard culture results. These results are all generated in 2 h or less of assay time and represent a strong preliminary dataset.

Conclusions

This 2 h portable, novel, phenotypic AST profiling will produce informed and effective treatment options for medics, clinics and physician offices long before existing AST methods could return results.
P30 A longitudinal perspective of antimicrobial resistance evolution within urinary tract infection-based clinical trials
Authors: Aldridge Phillip , Tan Aaron , Spencer Alexandra , Vallée Maxime , Harding Chris , Hall Judith
Published: August 2023

Background

The mainstay treatments for urinary tract infections (UTIs) are nitrofurantoin and trimethoprim. The common route to acquire trimethoprim resistance (TriR) is via horizontal transfer of the trimethoprim-insensitive dihydrofolate reductase: dfrA. In contrast, nitrofurantoin resistance (NitR) requires the inactivation of two chromosomally encoded nitroreductases: nfsA and nfsB. The difference in antimicrobial resistance (AMR) evolution is reflected in community surveillance data: NitR incidence = ∼10% and for TriR > 30%. Longitudinal clinical UTI trials provide a unique opportunity to monitor in situ evolution of AMR and correlate its appearance to trial outcomes and the impact on uropathogens.

Objectives

To explore the in situ AMR evolution and its impact in Escherichia coli isolates from patients participating in the clinical trials: AnTIC and ALTAR. AnTIC was an open label randomized trial assessing the efficacy of antibiotic prophylaxis use in clean intermittent self-catheterizing patients. ALTAR compared the efficacy of the non-antibiotic alternative methenamine hippurate to antibiotic prophylaxis to treat recurrent UTIs.

Methods

The investigation of the evolution of nitrofurantoin and trimethoprim resistance in E. coli used general microbiology techniques, bioinformatic genome analysis and genetics to model known AMR mutations in susceptible E. coli strains.

Results

Trimethoprim resistance amongst E. coli trial isolates was driven by 14 out of ∼45 known dfrA allelic variants; the most common being dfrA1 and dfrA17. Growth analysis identified an allelic bias when strains were exposed to sub-MIC concentrations of trimethoprim. Growth rate analysis identified a 2%–10% slower doubling time for nitrofurantoin-resistant strains: NitS: 20.8 ± 0.7 min compared to NitR: 23 ± 0.8 min. Statistically, these data suggested no fitness advantage of evolved strains compared to the sensitive predecessor (P value = 0.13). Genetic manipulation of E. coli to mimic NitR evolution, however, supported a selective advantage.

Conclusions

Longitudinal sampling during antibiotic based clinical trials has provided a new perspective to the response of E. coli to UTI-related antibiotics. Correlation of nitrofurantoin response to pharmacokinetic data suggests that the low incidence of E. coli NitR is driven by selection not fitness. However, fitness correlates to dfrA allele carriage and could potentially be exploited to benefit the use of trimethoprim if other antibiotics are impeded by AMR.
P32 Performance of a novel molecular test designed for point-of-care UTI diagnosis
Authors: van der Goes Ayako , Diggle Joanna , Nieuwland Jeroen , Roula Ali , Hayhurst Emma
Published: August 2023

Objectives

To evaluate the performance of a novel LAMP-based molecular test for the diagnosis of UTIs. The Llusern Scientific UTI test system consists of a panel of six uropathogen tests, positive and negative controls and an analyser, ‘Lodestar DX’ (Figure 1). The analyser will read the reaction data and give the user a simple ‘positive’ or ‘negative’ read out for each uropathogen. The specific aim was to determine the sensitivity and specificity of the test system for the most common uropathogen, Escherichia coli. Figure 1.Lodestar DX.

Methods

In total, 149 urine samples received by Public Health Wales laboratories, Cardiff were randomly selected; 1 μL of each urine sample was added directly to each pre-made E. coli LAMP test. E. coli LAMP tests were placed into the Lodestar DX analyser and run. Results were shown and recorded after 40 minutes as ‘positive’ or ‘negative’ according to the decision of Lodestar's algorithm. LAMP results were compared to standard culture results and sensitivity and specificity calculated.

Results

Overall sensitivity of the E. coli LAMP test was 86.2%. Specificity was 88.3% (Table 1). Of the 14 samples positive in the LAMP test for E. coli but not recorded as E. coli using culture, 11 were from ‘mixed growth’ samples (Table 2). Table 1.Sensitivity and specificity of E. coli LAMP testLAMP positiveLAMP negativeTotalCulture positive25 (true positives)4 (false negatives)29Culture negative14 (false positives)106 (true negatives)120Total39110149Overall sensitivity((25/29) × 100) = 86.2%Overall specificity((106/120) × 100) = 88.3%  Table 2.Results of LAMP compared with culture resultsCulture resultnE. coli Lodestar LAMP resultpositiveinconclusivenegativeE. coli positive292504Other pathogen positive121011Mixed growth6111050No growth472045Total149390110

Conclusions

The Llusern Scientific UTI test system shows great promise as a point-of-care diagnostic tool. Sensitivity and specificity for E. coli was high and the test system may be better at diagnosing mixed infections which represent a high proportion of all culture results. The test system is easy to use with no sample processing and minimal training requirements. Test results are available in 40 min, compared to 24–72 h for culture results. The performance of the test system for the detection of other uropathogens (Klebsiella, Enterococcus, Pseudomonas, Proteus and S. saprophyticus) is ongoing. Sensitivity can be further improved by refining the test method.