Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa.

Introduction: Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum ß-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible. Methods: Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while bla PER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of bla PER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. Results: Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried bla PER. One isolate carried bla PER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their bla PER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum ß-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of bla PER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other ß-lactamsin the in vitro evolved isolate. Discussion: PER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other ß-lactams.

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Lesiones y enfermedades durante el campeonato sudamericano de baloncesto en silla de ruedas 2021: un estudio epidemiológico / Injuries and illnesses during the Wheelchair Basketball South America Championships 2021: an epidemiological stud

Introducción: Varias federaciones deportivas internacionales han implementado un sistema estandarizado de registro delesiones durante sus campeonatos. Sin embargo, muy pocos estudios han incorporado a deportistas con discapacidad durantelos principales campeonatos, aparte de los Juegos Paralímpicos. Por lo tanto, el objetivo de este estudio es evaluar la tasa ycaracterísticas de las enfermedades y lesiones durante el Campeonato Sudamericano de Baloncesto en Silla de Ruedas 2021. Material y método: Se solicitó a los cuerpos técnicos de los 11 equipos participantes (un total de 129 jugadores), quereportaran diariamente todas las afecciones ocurridas y sus características en un formulario estandarizado. Se calcularon lastasas de prevalencia e incidencia.Resultados: Se reportaron 108 afecciones, equivalentes a 83,7 por 100 jugadores [IC 95%: 67,9-99,5], con 8 afecciones detiempo perdido (6,2 por 100 jugadores [IC 95%: 1,9-10,5]) y un total de 74 lesiones de atención médica (57,4 por 100 juga-dores [IC 95%: 44,3-70,4]). Se informaron 15 enfermedades, y los sistemas orgánicos más afectados fueron el oftalmológico,gastrointestinal y genitourinario. Se registraron más lesiones durante los partidos (n=43). Las regiones más afectadas fueronhombro/clavícula (24,7%), mano/dedos (23,7%) y cuello/columna cervical (12,9%). Las afecciones más frecuentes fueron lascontracturas/calambres musculares (32,2%), y el mecanismo predominante fue el sobreuso (53,8%). Se reportó un 2,2% deconmociones producidas durante los entrenamientos. La mayoría de los eventos registrados fueron sin pérdida de tiempo ycon retorno a la plena participación entre cero y un día. Conclusión: El seguimiento de problemas de salud durante las competiciones es esencial para determinar los factores deriesgo de lesiones específicas del deporte, y se debe implementar un enfoque complejo para el reconocimiento de sus carac-terísticas en jugadores de baloncesto en silla de ruedas.(AU)

Introduction: Several international sports federations have implemented a standardized injury registration system duringtheir championships. However, very few studies have included athletes with disabilities during major competitions, apart fromthe Paralympic Games. Therefore, the objective of this study is to evaluate the rate and characteristics of illnesses and injuriesduring the 2021 South America Wheelchair Basketball Championships.Material and method: The coaching staff of the 11 participating teams (a total of 129 players) were asked to report dailyall the health problems that have occurred and their characteristics in a standardized form. Prevalence and incidence rateswere calculated.Results: In this study 108 health problems were reported, equivalent to 83.7 per 100 players [95% CI: 67.9-99.5], with 8 time-loss health problems (6.2 per 100 players [95% CI: 1.9-10.5]) and a total of 74 medical attention injuries (57.4 per 100 players[95% CI :44.3-70.4]). Were reported 15 diseases, and the most affected organ systems were ophthalmologic, gastrointestinal,and genitourinary. More injuries were recorded during matches (n=43). The most affected regions were shoulder/clavicle(24.7%), hand/fingers (23.7%) and neck/cervical spine (12.9%). The most frequent conditions were muscle contractures/cramps (32.2%), and the predominant mechanism was overuse (53.8%). 2.2% of concussions produced during training werereported. Most of the recorded events were without time loss and with return to full participation between zero and one day.Conclusion: Monitoring of health problems during competitions is essential to determine sport-specific injury risk factors,and a complex approach should be implemented for the recognition of their characteristics in wheelchair basketball players.In this way, adequate preventive measures can be developed.(AU)

Acquisition of resistance to ceftazidime-avibactam during infection treatment in Pseudomonas aeruginosa through D179Y mutation in one of two blaKPC-2 gene copies without losing carbapenem resistance.

Ceftazidime/Avibactam (CAZ/AVI) is frequently used to treat KPC-producing Pseudomonas aeruginosa (KPC-PA) and Enterobacterales. CAZ/AVI resistance is driven by several mechanisms. In P. aeruginosa this mainly occurs through alteration of AmpC, porins, and/or efflux pump overexpression, whereas in Enterobacterales it frequently occurs through D179Y substitution in the active site of KPC enzyme. This aminoacid change abolishes AVI binding to the KPC active site, hence inhibition is impaired. However, this substitution also decreases KPC-mediated resistance to carbapenems ("see-saw" effect). The goal of this work was to characterize the in vivo acquisition of CAZ/AVI resistance through D179Y substitution in a KPC-PA isolated from a hospitalized patient after CAZ/AVI treatment. Two KPC-PA isolates were obtained. The first isolate, PA-1, was obtained before CAZ/AVI treatment and was susceptible to CAZ/AVI. The second isolate, PA-2, was obtained after CAZ/AVI treatment and exhibited high-level CAZ/AVI resistance. Characterization of isolates PA-1 and PA-2 was performed through short and long-read whole genome sequencing analysis. The hybrid assembly showed that PA-1 and PA-2A had a single plasmid of 54,030 bp, named pPA-1 and pPA-2 respectively. Each plasmid harbored two copies of the bla KPC-containing Tn4401b transposon. However, while pPA-1 carried two copies of bla KPC-2, pPA-2 had one copy of bla KPC-2 and one copy of bla KPC-33, the allele with the D179Y substitution. Interestingly, isolate PA-2 did not exhibit the "see-saw" effect. The bla KPC-33 allele was detected only through hybrid assembly using a long-read-first approach. The present work describes a KPC-PA isolate harboring a plasmid-borne CAZ/AVI resistance mechanism based on two copies of bla KPC-2-Tn4401b and D179Y mutation in one of them, that is not associated with loss of resistance to carbapenems. These findings highlight the usefulness of a fine-tuned combined analysis of short and long-read data to detect similar emerging resistance mechanisms.