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José Ignacio Fernández-Vigo,1 Inés Contreras,2 María José Crespo,3 Carlos Beckford,4 Ignacio Flores-Moreno,5 Rosario Cobo-Soriano,6 Jesús Pareja,7 María Dolores Martín,8 Luis Moreno,9 Luis Arrevola-Velasco10 1Deparment of Ophthalmology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain; 2Deparment of Ophthalmology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS) and Clínica Rementería, Madrid, Spain; 3Department of Ophthalmology, Hospital Universitario Infanta Leonor, Madrid, Spain; 4Department of Ophthalmology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; 5Department of Ophthalmology, Hospital Universitario Puerta de Hierro, Madrid, Spain; 6Department of Ophthalmology, Hospital Universitario Henares, Universidad Francisco de Vitoria, Madrid, Spain; 7Department of Ophthalmology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 8Department of Ophthalmology, Hospital Infanta Cristina, Madrid, Spain; 9Department of Ophthalmology, Hospital 12 de Octubre, Madrid, Spain; 10Department of Ophthalmology, Clinica Baviera Instituto Oftalmológico Europeo, Madrid, SpainCorrespondence: Luis Arrevola-Velasco, Department of Ophthalmology, Clínica Baviera Instituto Oftalmológico Europeo, P.° de la Castellana, 20, Madrid, 28046, Spain, Tel +34 917 82 03 60, Email larrevola@telefonica.netPurpose: The treatment of diabetic macular edema (DME) has evolved rapidly in the past decade, highlighting the need to address the challenges of routine clinical practice decision-making through expert consensus agreements.Methods: After a literature review and discussion of real-world experience on DME management, a group of ten retina specialists agreed on a consensus of recommendations for the most appropriate management of DME patients using vascular endothelial growth factor inhibitors (anti-VEGF) in Spain.Results: The panel recommended early treatment initiation in DME patients with worse baseline visual acuity (VA) to maintain or improve outcome. For patients with good VA, an observation strategy was recommended, considering the presence of diabetic retinopathy, optical coherence tomography biomarkers, and impact on patient’s quality of life. Based on the available evidence and clinical experience, the panel recommended the use of anti-VEGF intensive loading doses with the objective of achieving anatomic and visual responses as soon as possible, followed by a Treat & Extend (T&E) strategy to maintain VA improvement. Aflibercept was recommended for patients with a baseline decimal VA < 0.5, followed by a T&E strategy, including the possibility to extend frequency of injections up to 16 weeks.Conclusion: An expert panel proposes a consensus for the management of DME in Spain. Early treatment initiation with anti-VEGF in DME patients is recommended to maintain or improve VA; aflibercept is recommended for patients with a poor baseline VA.Keywords: diabetic macular edema, clinical practice patterns, intravitreal injections, consensus

Dan Gordon,1 Sarah Wightman,2 Itay Basevitch,1 James Johnstone,1 Carolina Espejo-Sanchez,1 Chelsea Beckford,1 Mariette Boal,1 Adrian Scruton,1 Mike Ferrandino,1 Viviane Merzbach1 1Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, 2The Flying Runner, Cambridge, UK Purpose: The aim of this study was to examine the physical and training characteristics of recreational marathon runners within finish time bandings (2.5–3 h, 3–3.5 h, 3.5–4 h, 4–4.5 h and >4.5 h).Materials and methods: A total of 97 recreational marathon runners (age 42.4 ± 9.9 years; mass 69.2 ± 11.3 kg; stature 172.8 ± 9.1 cm), with a marathon finish time of 229.1 ± 48.7 min, of whom n = 34 were female and n = 63 were male, completed an incremental treadmill test for the determination of lactate threshold (LT1), lactate turn point (LT2) and running economy (RE). Following a 7-min recovery, they completed a test to volitional exhaustion starting at LT2 for the assessment of VO2max. In addition, all participants completed a questionnaire gathering information on their current training regimes exploring weekly distances, training frequencies, types of sessions, longest run in a week, with estimations of training speed, and load and volume derived from these data.Results: Training frequency was shown to be significantly greater for the 2.5–3 h group compared to the 3.5–4 h runners (P < 0.001) and >4.5 h group (P = 0.004), while distance per session (km⋅session–1) was significantly greater for the 2.5–3 h group (16.1 ± 4.2) compared to the 3.5–4 h group (15.5 ± 5.2; P = 0.01) and >4.5 h group (10.3 ± 2.6; P = 0.001). Race speed correlated with LT1 (r = 0.791), LT2 (r = 0.721) and distance per session (r = 0.563).Conclusion: The data highlight profound differences for key components of marathon running (VO2max, LT1, LT2, RE and % VO2max) within a group of recreational runners with the discriminating training variables being training frequency and the absolute training speed. Keywords: endurance running, nonelite, workout structures, maximal oxygen uptake, running economy, aerobic capacity

This study examined rates of psychiatric disorders and impairment in 283 children, aged 6 to 17, of 69 Caucasian, 45 African-American, and 47 Hispanic-American methadone maintenance patients. Children were evaluated by direct and/or parental interview with the K-SADS-E. Final DSM-III-R diagnoses and Global Assessment Scale (C-GAS) were assigned by best estimate. Substantial lifetime prevalences of mood (21%), anxiety (24%) and disruptive disorders (30%), school problems (37%), and global impairment (C-GAS < 61) (25%) were observed in the children of opiate-dependent patients. There were few differences between ethnic groups. Effects of proband gender and major depression and their interactions with ethnicity on risk for childhood psychopathology were also examined. The results suggest children of patients in treatment for opiate dependence from diverse ethnic groups are at risk for psychopathology. Programs for early detection and intervention should be devised and evaluated. [ABSTRACT FROM AUTHOR]

Nosocomial infections caused by multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) pathogens are on the rise. However, the virulence strategies employed by these pathogens remain elusive. Here, we study the interaction of ECC clinical isolates with human serum to define how this pathogen evades the antimicrobial action of complement, one of the first lines of host-mediated immune defense. We identified a small number of serum-sensitive strains, including Enterobacter hormaechei strain NR3055, which we exploited for the in vitro selection of serum-resistant clones. Comparative genomics between the serum-sensitive NR3055 strain and the isolated serum-resistant clones revealed a premature stop codon in the wzy gene of the capsular polysaccharide biosynthesis locus of NR3055. The complementation of wzy conferred serum resistance to NR3055, prevented the deposition of complement proteins on the bacterial surface, inhibited phagocytosis by human neutrophils, and rendered the bacteria virulent in a mouse model of peritonitis. Mice exposed to a nonlethal dose of encapsulated NR3055 were protected from subsequent lethal infections by encapsulated NR3055, whereas mice that were previously exposed to unencapsulated NR3055 succumbed to infection. Thus, capsule is a key immune evasion determinant for E. hormaechei , and it is a potential target for prophylactics and therapeutics to combat these increasingly MDR human pathogens. IMPORTANCE Infections caused by antimicrobial resistant bacteria are of increasing concern, especially those due to carbapenem-resistant Enterobacteriaceae pathogens. Included in this group are species of the Enterobacter cloacae complex, regarding which there is a paucity of knowledge on the infection biology of the pathogens, despite their clinical relevance. In this study, we combine techniques in comparative genomics, bacterial genetics, and diverse models of infection to establish capsule as an important mechanism of Enterobacter pathogens to resist the antibacterial activity of serum, a first line of host defense against bacterial infections. We also show that immune memory targeting the Enterobacter capsule protects against lethal infection. The further characterization of Enterobacter infection biology and the immune response to infection are needed for the development of therapies and preventative interventions targeting these highly antibiotic resistant pathogens.

Purpose: Among the main causes of blindness and severe vision loss are age-related macular degeneration, diabetic macular oedema, and retinal vein occlusion. The «Do Not Do» recommendations are strategies to improve quality of care and optimise healthcare costs. The aim of this study was to establish, by consensus, practices of low value in the above-mentioned pathologies, in addition to estimating their occurrence., Materials and Methods: Mixed methods study including a first phase of consensus of a multidisciplinary panel of experts using the Nominal Group technique. In the second phase, a retrospective observational study was conducted, by conducting a review of medical records., Results: A total of 7 recommendations were established for age-related macular degeneration, 4 for diabetic macular oedema, and 5 for retinal vein occlusion. A total of 1,012 medical records were reviewed by the 4 participating hospitals. The review of medical records revealed that agreed «Do Not Do's» occurred in a range between 0.6% and 31.4% of the cases included in the study., Conclusions: This study identified «Do Not Do» recommendations in these pathologies that occur relatively often in clinical practice. It is necessary to review the healthcare processes that will enable these practices to be eradicated, and the quality of care to be improved., (Copyright © 2021 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Whole-genome sequencing (WGS) is increasingly used to map the spread of bacterial and viral pathogens in nosocomial settings. A limiting factor for more widespread adoption of WGS for hospital infection prevention practices is the availability of standardized tools for genomic epidemiology., Methods: We developed the Pathogen Sequencing Phylogenomic Outbreak Toolkit (PathoSPOT) to automate integration of genomic and medical record data for rapid detection and tracing of nosocomial outbreaks. To demonstrate its capabilities, we applied PathoSPOT to complete genome surveillance data of 197 MRSA bacteremia cases from two hospitals during a 2-year period., Results: PathoSPOT identified 8 clonal clusters encompassing 33 patients (16.8% of cases), none of which had been recognized by standard practices. The largest cluster corresponded to a prolonged outbreak of a hospital-associated MRSA clone among 16 adults, spanning 9 wards over a period of 21 months. Analysis of precise timeline and location data with our toolkit suggested that an initial exposure event in a single ward led to infection and long-term colonization of multiple patients, followed by transmissions to other patients during recurrent hospitalizations., Conclusions: We demonstrate that PathoSPOT genomic surveillance enables the detection of complex transmission chains that are not readily apparent from epidemiological data and that contribute significantly to morbidity and mortality, enabling more effective intervention strategies.

The purpose was to create and assess the impact of food literacy curriculum alongside a centrally procured school snack program among grade five students in Southwestern Ontario, Canada. Grade five students ( N = 287) from five intervention and three controls schools participated in an 8-week food delivery program. In addition to the food delivery program, intervention schools received a resource kit and access to 42 multidisciplinary food literacy lesson plans using the produce delivered as part of the food delivery program. Participants completed matched pre- and post-test online surveys to assess fruit and vegetable intake, knowledge, preferences, and attitudes. Descriptive analyses and changes in scores between the intervention and control schools were assessed using one-way ANOVAs, paired samples t -tests, and McNemar's tests. In total, there were 220 participants that completed both the pre- and post-test surveys. There was a significant improvement in fruit and vegetable intake ( p = 0.038), yet no differences in knowledge of the recommended number of food group servings, knowledge of food groups, or fruit and vegetable preferences or attitudes were observed. Integrating nutrition lesson plans within core curricula classes (e.g., math, science, and literacy) can lead to modest increases in fruit and vegetable intake.

Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored. Here, we perform a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high level of epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity, the corresponding gene of which is highly conserved across our dataset and in all of the approximately 300 global C. difficile genomes examined. Inactivation of the methyltransferase gene negatively impacts sporulation, a key step in C. difficile disease transmission, and these results are consistently supported by multiomics data, genetic experiments and a mouse colonization model. Further experimental and transcriptomic analyses suggest that epigenetic regulation is associated with cell length, biofilm formation and host colonization. These findings provide a unique epigenetic dimension to characterize medically relevant biological processes in this important pathogen. This study also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomic studies.

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence., (Copyright © 2019 Sullivan et al.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of health care-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones., Methods: Comprehensive clinical data from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones were compared using logistic regression., Results: Molecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (n = 117) and CC8 (n = 110). MRSA BSIs were associated with a 90-day mortality rate of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; P < .001) and in those of nonwhite race (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.51-7.87; P = .003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR, 5.96; 95% CI, 1.51-23.50; P = .01)., Conclusions: The clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen are crucial to inform management and prevent disease., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: To review the available data on non-surgical management for neurogenic bladder in patients with spinal cord injury (SCI). Before the introduction of urinary catheters and antibiotics, neurogenic bladder was one of the main culprits for death in those patients with SCI. Currently, the management of neurogenic bladder is focused in improving quality of life and preserving renal function., Methods: A literature review was performed and therapeutic management for neurogenic bladder was divided in six sections: (1) intermittent bladder catheterization; (2) indwelling catheters; (3) condom catheter drainage; (4) reflex voiding and bladder expression with Valsalva or Credé; (5) oral drug therapy of the spinal cord injured bladder; and (6) botulinum neurotoxin (BoNT)., Results: Intermittent catheterization is recommended as the preferable method for management of neurogenic bladder in patients with SCI based on limited high-quality data. However, this may not be feasible or available to all and other alternative options include condom catheter drainage or indwelling catheters such as urethral catheters or suprapubic tube, reflex voiding, and bladder expression with Valsalva or Credé. Non-invasive medical therapies are the key to improve incontinence, urodynamic parameters, and quality of life in this population. Botulinum neurotoxin has revolutionized the management of neurogenic bladder in the last two decades decreasing the need for reconstruction or diversion., Conclusion: The Joint SIU-ICUD (Société Internationale d'Urologie) (International Consultation on Urological Diseases) International Consultation reviewed the available presented data and provided specific conclusions and recommendations for each non-surgical urologic method to address neurogenic bladder after SCI.

[This corrects the article DOI: 10.1155/2017/5474916.].

Whole-genome sequencing was used to examine a persistent Enterococcus faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in fabF , encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug., (Copyright © 2018 Chacko et al.)

The aim of this study was to determine the aerobic contribution to upper body and lower body Wingate Anaerobic tests (WAnT). Eight nonspecifically trained males volunteered to take part in this study. Participants undertook incremental exercise tests for peak oxygen uptake and two 30-s WAnT (habituation and experimental) for both the upper and lower body. The resistive loadings used were 0.040 and 0.075 kg·kg body mass(-1), respectively. Peak power output (PPO) and mean power output (MPO) were calculated for each WAnT. The aerobic contribution of each WAnT was assessed using breath by breath expired gas analysis. Peak oxygen uptake was lower for the upper body when compared with the lower body (P = 0.001). Similarly, PPO and MPO were greater for the lower body (both P < 0.001). Absolute oxygen uptake during the upper body WAnT was lower than for the lower body (P = 0.013), whereas relative oxygen uptake (% peak oxygen uptake) was similar (P = 0.997). The mean aerobic contribution for the upper body WAnT (43.5% ± 29.3%) was greater than for the lower body (29.4% ± 15.8%; P < 0.001). The greater aerobic contribution to the WAnT observed for the upper body in comparison with the lower body is likely due to methodological differences in upper and lower body WAnT protocols and potentially differences in anaerobic power production and exercise efficiency. The results of this study suggest that differences may exist for the aerobic contribution of upper and lower body Wingate anaerobic tests.

Objective: Assessment of four eradicating patterns of 6 and 12 days duration with new triple therapies adapted to our environment., Patients: After an endoscopic diagnosis of Duodenal or Gastric Ulcer, and the confirmation of the presence of Helicobacter pylori using a rapid urease test in antral biopsies, 274 patients were treated with one of four eradicating therapies, verifying its efficacy with the C-13 urea breath test, at least one month after the end of the treatment and 10 days after withdrawal of proton pump inhibitors., Results: Maximum eradicating efficacy was achieved with Omeprazole (20 mg/12 hours), Clarithromycin (500 mg/12 hours) and Amoxycillin (1 g/12 hours), given for 12 days (96.6%), and Omeprazole (20 mg/12 hours), Tinidazole (500 mg/12 hours) and Clarithromycin (500 mg/12 hours), also given for 12 days (95.2%). The same drugs and doses, when given during six days, achieved percentages of 78.3% and 82.2% respectively. Results with Tinidazole suggest lack of resistance to this drug in the Community of Madrid.

Background: Familial exudative vitreoretinopathy is an uncommon heredodegenerative disease with different types of inheritance and degrees of severity., Methods: Findings in five affected members of a family in which the X-linked mode of inheritance of familial exudative vitreoretinopathy is present are discussed., Results: Patients presented with characteristic retinal exudative tractional detachment, temporal retinal vessel traction, capillary dilatation, neovascularization, and vitreous veils., Conclusion: A review of the 21 cases of X-linked familial exudative vitreoretinopathy reported to date indicates a worse outcome in this mode of inheritance than in cases of autosomal dominant inheritance.