Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.

Walking improvement in chronic incomplete spinal cord injury with exoskeleton robotic training (WISE): a randomized controlled trial.

STUDY DESIGN: Clinical trial. OBJECTIVE: To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI). SETTING: Outpatient rehabilitation or research institute. METHODS: Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI (>1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary outcomes included: Timed-Up-and-Go (TUG), 6-min walk test (6MWT), Walking Index for Spinal Cord Injury (WISCI-II) (assistance and devices), and treating therapist NASA-Task Load Index. RESULTS: Twenty-five participants completed the assessments and training as assigned (9 Ekso, 10 Active Control, 6 Passive Control). Mean change in gait speed at the primary endpoint was not statistically significant. The proportion of participants with improvement in clinical ambulation category from home to community speed post-intervention was greatest in the Ekso group (>1/2 Ekso, 1/3 Active Control, 0 Passive Control, p < 0.05). Improvements in secondary outcome measures were not significant. CONCLUSIONS: Twelve weeks of exoskeleton robotic training in chronic SCI participants with independent stepping ability at baseline can improve clinical ambulatory status. Improvements in raw gait speed were not statistically significant at the group level, which may guide future trials for participant inclusion criteria. While generally safe and tolerable, larger gains in ambulation might be associated with higher risk for non-serious adverse events.

Chasing Weak Forces: Hierarchically Assembled Helicates as a Probe for the Evaluation of the Energetics of Weak Interactions.

London dispersion forces are the weakest interactions between molecules. Because of this, their influence on chemical processes is often low, but can definitely not be ignored, and even becomes important in cases of molecules with large contact surfaces. Hierarchically assembled dinuclear titanium(IV) helicates represent a rare example in which the direct observation of London dispersion forces is possible in solution even in the presence of strong cohesive solvent effects. Hereby, the dispersion forces do not unlimitedly support the formation of the dimeric complexes. Although they have some favorable enthalpic contribution to the dimerization of the monomeric complex units, large flexible substituents become conformationally restricted by the interactions leading to an entropic disadvantage. The dimeric helicates are entropically destabilized.

Comparison of Costs, Re-Intervention Rates, and Length of Hospital Stay for Three Uterus Sparing Interventions for Uterine Fibroids: A 2-Year Retrospective Claims Analysis.

Purpose: To describe two-year post-operative outcomes, and healthcare utilization of three uterus-sparing interventions used to treat women with intramural and/or subserosal uterine fibroids. Subjects and Methods: This was a post-market, randomized, prospective, multi-center, longitudinal, interventional, and comparative clinical study to evaluate the costs and health outcomes of LAP-RFA vs the standard uterine conserving technologies (myomectomy and UAE) for the treatment of symptomatic uterine fibroids in women who desire uterine conservation. For this RCT study, 54 subjects were randomized on a 1:1 ratio across the three procedures and followed out to two years. Their results were compared to retrospective US insurance claims from the IBM MarketScan® Commercial Database from 2017-2020 for 96,854 women who underwent a uterus-sparing procedure for fibroids. Results: Mean ambulatory surgical center costs and the mean out-patient hospital costs were lowest for LAP-RFA ($13,134 and $14,428) and highest for UAE ($28,214 and $19,131). The total two-year re-intervention rate of any subsequent procedure (AM, LM, LAP-RFA, or UAE) was lowest in AM group (0%) followed by LM (4.2%), LAP-RFA (11%), and UAE (33%). Mean peri-operative reintervention costs and the mean reintervention total costs were $2429 and $5939 for LAP-RFA, $2122 and $8368 for LM, $4410 and $11,942 for AM, and $8113 and $46,692 for UAE subjects. In the RCT study, the average length of hospital stay was significantly less for the LAP-RFA group subjects (8.2 hours) in contrast to both the laparoscopic myomectomy group subjects (16.0 hours) and the abdominal myomectomy group subjects (33.6 hours). Despite the small numbers, two-year reintervention rates followed a similar pattern as the IBM MarketScan data. Conclusion: In comparing these three non-invasive approaches, LAP-RFA was associated with the lowest peri-operative cost, and UAE was associated with the highest peri-operative cost. Further studies are needed to assess the cost, effectiveness, and subject satisfaction with each procedure.

Carbonic anhydrase regulation and CO(2) sensing in the fungal pathogen Candida glabrata involves a novel Rca1p ortholog.

Carbon dioxide (CO2) is a ubiquitous gas present at 0.0391% in atmospheric air and 5.5% in human blood. It forms part of numerous carboxylation and decarboxylation reactions carried out in every cell. Carbonic anhydrases (CA) enhance the hydration of CO2 to generate bicarbonate, which is subsequently used in cellular metabolism. In microorganisms, including the yeasts Candida albicans and Saccharomyces cerevisiae, inactivation of CA leads to a growth defect in air, which is complemented in an atmosphere enriched with CO2. In this study we characterize the CA from the fungal pathogen of humans Candida glabrata, CgNce103p, and report a comparable phenotype following its inactivation. Furthermore, we show that expression of the C. glabrata CA is strongly regulated by environmental CO2 at both the protein and transcript level. Similar to what we have previously reported for C. albicans and S. cerevisiae, C. glabrata CA regulation by CO2 is independent from the cAMP-PKA pathway and requires the novel bZIP transcription factor CgRca1p. We show that CgRca1p is an ortholog of the transcription factors Rca1p from C. albicans and Cst6p from S. cerevisiae and prove that CA induction in low CO2 involves the conserved DNA-binding motif TGACGTCA located on this C. glabrata promoter. However, in contrast to what is found in C. albicans CgRca1p expression itself is not affected by CO2. Although our results suggest a high level of similarity between the CO2 sensing pathways from C. glabrata, S. cerevisiae and C. albicans, they also point out significant intrinsic differences.

Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial.

INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss. METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice. ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study. TRIAL REGISTRATION NUMBER: ISRCTN13704894. PROTOCOL VERSION: V 1.3.

Community structure of soil fungi in a novel perennial crop monoculture, annual agriculture, and native prairie reconstruction.

The use of perennial crop species in agricultural systems may increase ecosystem services and sustainability. Because soil microbial communities play a major role in many processes on which ecosystem services and sustainability depend, characterization of soil community structure in novel perennial crop systems is necessary to understand potential shifts in function and crop responses. Here, we characterized soil fungal community composition at two depths (0-10 and 10-30 cm) in replicated, long-term plots containing one of three different cropping systems: a tilled three-crop rotation of annual crops, a novel perennial crop monoculture (Intermediate wheatgrass, which produces the grain Kernza®), and a native prairie reconstruction. The overall fungal community was similar under the perennial monoculture and native vegetation, but both were distinct from those in annual agriculture. The mutualist and saprotrophic community subsets mirrored differences of the overall community, but pathogens were similar among cropping systems. Depth structured overall communities as well as each functional group subset. These results reinforce studies showing strong effects of tillage and sampling depth on soil community structure and suggest plant species diversity may play a weaker role. Similarities in the overall and functional fungal communities between the perennial monoculture and native vegetation suggest Kernza® cropping systems have the potential to mimic reconstructed natural systems.

The transcriptional regulator CprK detects chlorination by combining direct and indirect readout mechanisms.

The transcriptional regulator CprK controls the expression of the reductive dehalogenase CprA in organohalide-respiring bacteria. Desulfitobacterium hafniense CprA catalyses the reductive dechlorination of the terminal electron acceptor o-chlorophenol acetic acid, generating the phenol acetic acid product. It has been shown that CprK has ability to distinguish between the chlorinated CprA substrate and the de-halogenated end product, with an estimated an estimated 10(4)-fold difference in affinity. Using a green fluorescent protein GFPUV-based transcriptional reporter system, we establish that CprK can sense o-chlorophenol acetic acid at the nanomolar level, whereas phenol acetic acid leads to transcriptional activation only when approaching micromolar levels. A structure-activity relationship study, using a range of o-chlorophenol acetic-acid-related compounds and key CprK mutants, combined with pKa calculations on the effector binding site, suggests that the sensitive detection of chlorination is achieved through a combination of direct and indirect readout mechanisms. Both the physical presence of the bulky chloride substituent as well as the accompanying electronic effects lowering the inherent phenol pKa are required for high affinity. Indeed, transcriptional activation by CprK appears strictly dependent on establishing a phenolate-K133 salt bridge interaction, rather than on the presence of a halogen atom per se. As K133 is strictly conserved within the CprK family, our data suggest that physiological function and future applications in biosensing are probably restricted to phenolic compounds.

(Re)criação do olhar: oficinas estéticas com crianças com deficiência visual / (Re)creation of the look: aesthetic workshops with children with visual impairment / (Re)crear de la perspectiva: talleres de estética con niños con deficiencia visual

A partir da apresentação de uma experiência de (re)criação do olhar mediada por diferentes linguagens artísticas, este texto problematiza modos de (vi) ver de crianças com deficiência visual. Consideramos o pesquisar como acontecimento no encontro com pessoas; um processo dialógico que possibilita o "pesquisarCOM". Para tanto, desenvolvemos uma oficina estética que foi registrada por meio de filmagens, fotografias e registros em diário de campo, e constituem o conjunto de informações analisadas. Os resultados permitiram constatar que a deficiência visual possibilita à pessoa ver com os olhos dos outros e com todo o corpo, levando-a a usar, para a construção de imagens intrapsicológicas e fotográficas, a linguagem verbal, a imaginação, a emoção, juntamente com outros processos psicológicos

From the presentation of an experience of (re)creating the look mediated by different artistic languages, this text questions ways of living and seeing of children with visual impairment. We considered the research as a happening in meeting with people; a dialogical process that allows the search WITH. Since then, we developed an aesthetic workshop which was documented through filming, photographs and daily field reports and constitute the set of analyzed information. The results demonstrated that visual impairment makes it possible for a person to see through the eyes of the other and with its whole body, causing it to use for the construction of intrapsychological and photographical images, the verbal language, the imagination, the emotion, along with other psychological process

A partir de la presentación de una experiencia de (re)creación de la mirada por medio de diferentes lenguajes artísticos, este texto problematiza los modos de (vivir) ver de los niños con deficiencia visual. Consideramos la investigación como un acontecimiento en el encuentro con personas; un proceso dialógico que permite investigar CON. Para eso, desarrollamos un taller estético registrado a través de filmaciones, fotografías y registros en diario de campo, y constituyen toda la información analizada. Los resultados permitieron constatar que la deficiencia visual permite que la persona vea con los ojos de los otros y con todo el cuerpo, llevándola a usar, para la construcción de imágenes intrapsicológicas y fotográficas, el lenguaje verbal, la imaginación, la emoción, juntamente con otros procesos psicológicos