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1.
Autism ; : 13623613241271950, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143667

RESUMEN

LAY ABSTRACT: Selective attention to auditory input is reflected in the brain by an electric amplitude called the P3b amplitude, which is measured using electroencephalography. Previous research has shown that children and adolescents with autism have an attenuated P3b amplitude when they have to attend specific sounds while ignoring other sounds. However, it is unknown whether a reduced P3b amplitude in autistic children and adolescents is associated with their autism features, daily functioning and/or cognitive functions. This study aimed to examine these questions. Therefore, we assessed selective attention to auditory input in 57 children with autism aged 7-14 years and 57 neurotypically developing controls while measuring their brain activity with electroencephalography. Participants further underwent cognitive assessment, and parents reported on autistic traits and daily functioning. As expected, children with autism had lower P3b amplitude compared to their neurotypical peers. Importantly, an attenuated P3b amplitude was associated with more parent-reported social-communication problems and difficulties with daily functioning. Children with autism further had reduced processing speed of visual input, which also was coupled to a lower P3b amplitude. In conclusion, we found attenuated P3b amplitude in children with autism performing an auditory selective attention task, which was related to difficulties with processing visual input and allocating attentional resources critical for social and daily functioning. The results suggest that autistic children are more vulnerable to being disturbed when the environment is filled with conflicting sensory input.

2.
J Wound Ostomy Continence Nurs ; 51(4): 303-311, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39037163

RESUMEN

PURPOSE: The purpose of the study was to investigate the fit of a two-piece pouching system with a concave-shaped skin barrier on people with an outward peristomal body profile and its effect on leakage, wear time, and quality of life (QoL) related to using an ostomy product. DESIGN: Randomized, controlled, open-label, cross-over trial. SUBJECTS AND SETTINGS: The sample comprised 53 subjects with outward peristomal body profiles and problems with leakage of ostomy effluent from their pouching system. Participants were randomized to the concave two-piece pouching system or a comparator (two-piece pouching system with a flat skin barrier) for 3 weeks. Subjects were then crossed over to the opposite skin barrier for an additional 3 weeks. The study was conducted in Denmark, Norway, Germany, and the Netherlands; data were collected in multiple ambulatory clinics or during home visits. METHODS: The primary end point was the ability of the skin barrier to fit body contours; secondary outcomes were leakage of effluent from the pouching system, wear time, and QoL related to using an ostomy product via the validated Ostomy-Q questionnaire. Primary comparisons between concave and comparator pouching systems were evaluated using proportional odds models and mixed models taking test period into account. RESULTS: Analysis included randomized subjects who had been exposed to at least one product and with information on at least one end point (full-analysis-set, n = 52). The concave pouching system provided a better fit to body contours than the comparator (P< .001) and reduced the degree of leakage underneath the skin barrier (LS mean difference = -1.84, 95% CI -3.31 to -0.37; P = .016). Participants experienced fewer episodes of leakage outside the skin barrier when using concave versus comparator pouching system (13.0% vs. 26.7%, respectively). Participants reported significant improvements in QoL (LS mean difference = 14.3; 95% CI 9.4 to 19.2; P < .001). No significant difference in wear time between skin barrier shapes was reported. CONCLUSIONS: Study findings indicate that a pouching system with a concave skin barrier achieved a better body fit on people with an outward peristomal body profile and resulted in fewer leakage incidents and higher QoL compared to using a pouching system with a flat skin barrier.


Asunto(s)
Estudios Cruzados , Calidad de Vida , Humanos , Calidad de Vida/psicología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Países Bajos , Estomía/métodos , Estomía/efectos adversos , Estomía/instrumentación , Dinamarca , Alemania , Noruega , Encuestas y Cuestionarios , Estomas Quirúrgicos/efectos adversos
3.
Artículo en Inglés | MEDLINE | ID: mdl-38981497

RESUMEN

BACKGROUND: Nosocomial infections contribute significantly to mortality and morbidity in burn patients. Selective decontamination of the digestive tract is an infection prevention measure that has been shown to improve survival in mechanically ventilated intensive care unit (ICU) patients. It has been hypothesized that burn patients may benefit from selective decontamination of the digestive tract. METHODS/DESIGN: We will conduct a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials (RCTs) assessing the patient-important effects of selective decontamination of the digestive tract in burn patients, as compared with placebo or no intervention/standard of care. The primary outcome will be 30-day mortality. Secondary outcomes include serious adverse events, anti-microbial resistance, pneumonia, blood stream infections, ICU- and hospital-free days and 90-day mortality. We will search the following databases: CENTRAL, MEDLINE, EMBASE, BIOSIS, Web of Science and CINAHL and follow the recommendations provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The certainty of evidence will be assessed according to the GRADE approach: Grading of Recommendations Assessment, Development and Evaluation. DISCUSSION: There is clinical equipoise about the use of selective decontamination of the digestive tract in burn patients. In the outlined systematic review and meta-analysis, we will assess the desirable and undesirable effects of selective decontamination of the digestive tract in burn patients.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39008199

RESUMEN

Parent-child informant discrepancies on psychopathology provide important knowledge on the parent-child relationship and the child's mental health, but mechanisms underlying parent-child informant discrepancies are largely unknown. Therefore, we investigated the relationship between attachment problems and mentalizing capacity and parent-child informant discrepancies on borderline personality disorder (BPD) severity, internalizing, and externalizing pathology in a clinical sample of 91 adolescent girls with BPD and their parents. Results showed that more attachment problems to parents and peers were related to adolescents reporting more severe BPD than parents. Adolescents who described more internalizing symptoms relative to parents, reported more parental attachment problems, but enhanced peer attachment, suggesting those adolescents who do not feel recognized by their parents might turn to their friends. When parents rated adolescents higher on externalizing behaviors, the adolescent reported more attachment problems to parents and lower mentalizing capacity, indicating that this sub-group of adolescents may reflect less about how their behavior affects others.

5.
J Clin Exp Neuropsychol ; 46(3): 218-232, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38704611

RESUMEN

Increased schizotypal traits have previously been associated with atypical semantic cognition in community samples. However, no study has yet examined whether adults diagnosed with schizotypal personality disorder (SPD) display atypical semantic fluency and memory. We hypothesized that 24 adults diagnosed with SPD would name more idiosyncratic words on the semantic fluency task and show decreased semantic recall for animal and fruit category words compared with 29 participants with borderline personality disorder (BPD) and a community sample of 96 age-matched controls. We examined whether atypical semantic cognition was specifically associated with disorganized and eccentric speech and thinking, or more broadly with pathological personality traits and personality functioning. Our main hypothesis was confirmed, as the SPD participants named more idiosyncratic words and recalled fewer semantically related words compared with controls. Surprisingly, participants with BPD likewise named more atypical words compared with controls. More idiosyncratic semantic fluency was associated with more eccentric speech and thinking. Increased idiosyncratic semantic fluency and reduced semantic recall were both coupled to increased detachment and lowered personality functioning, while reduced semantic recall further was related to increased interpersonal problems. Our findings suggest that persons with SPD, and to a lesser degree BPD, show atypical semantic cognition, which is associated with eccentric speech and thinking, and more broadly with impaired personality function, social withdrawal, and emotional flatness. The idiosyncratic semantic cognition may worsen difficulties with social reciprocity seen in SPD and BPD.


Asunto(s)
Trastorno de Personalidad Limítrofe , Trastorno de la Personalidad Esquizotípica , Semántica , Humanos , Femenino , Trastorno de Personalidad Limítrofe/fisiopatología , Trastorno de Personalidad Limítrofe/psicología , Trastorno de Personalidad Limítrofe/complicaciones , Masculino , Adulto , Trastorno de la Personalidad Esquizotípica/fisiopatología , Trastorno de la Personalidad Esquizotípica/complicaciones , Adulto Joven , Persona de Mediana Edad , Pruebas Neuropsicológicas , Recuerdo Mental/fisiología , Trastornos del Conocimiento/etiología
6.
Br J Nurs ; 32(16): S32-S41, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37682765

RESUMEN

BACKGROUND: Stoma surgery is a life-changing event and patients must subsequently make significant adjustments to their lives. AIM: The study set out to understand the level of interaction between patients and stoma care nurses (SCNs) in relation to preparing patients for stoma surgery and in adjustment to life with a stoma. METHODS: Retrospective, self-reported questionnaires for patients and SCNs. FINDINGS: Most patients (98%) with planned stoma surgery had pre-operative consultations with health professionals in contrast to 36% of patients with unplanned surgery, who did not. One third of patients with unplanned surgery did not feel prepared for life with a stoma based on the information provided during their hospital stay. Two thirds of the nurses reported having sufficient time to prepare patients for stoma surgery and to life with a stoma. CONCLUSION: SCNs are key in preparing patients for surgery and for life with a stoma. Variations in care were experienced by patients having planned versus unplanned surgeries.


Asunto(s)
Emociones , Enfermeras Clínicas , Humanos , Estudios Retrospectivos , Personal de Salud , Tiempo de Internación
7.
Children (Basel) ; 10(6)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37371224

RESUMEN

The International Classification of Diseases 11th Revision (ICD-11) introduces fundamentally new diagnostic descriptions for personality disorder and autism spectrum disorder. Instead of the traditional categorical taxonomies, both personality disorder and autism spectrum disorder are described as being on a continuum. Accumulating research has pointed out that, in some cases, adolescents with autism spectrum disorder are at risk of being confused with having a personality disorder, which particularly applies to female adolescents. Case reports describe how adult autistic women struggled with social and identity roles as children and adolescents, using compensatory strategies such as social imitation and other types of camouflaging. Furthermore, some adolescents with autism display emotion dysregulation and self-injury. The ICD-11 recognizes that features of autism spectrum disorder may resemble features of personality disorder, but the two diagnoses have not yet been formally compared to one another. The present article therefore sought to outline and discuss the overlap and boundaries between the ICD-11 definitions of personality disorder and autism spectrum disorder and propose guiding principles that may assist practitioners in differential diagnosis with female adolescents. We specifically highlight how aspects of the self and interpersonal functioning along with emotional, cognitive, and behavioral manifestations may overlap across the two diagnoses. Restricted, repetitive, and inflexible patterns of behavior, interests, and activities are core features of autism spectrum disorder, which may be masked or less pronounced in female adolescents. Collecting a developmental history of the early presence or absence of autistic features is vital for a conclusive diagnosis, including features that are typically camouflaged in females. A number of future directions for research and clinical practice are proposed.

8.
Microbiol Spectr ; 11(4): e0062523, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37289074

RESUMEN

Polyether ionophores are complex natural products known to transport various cations across biological membranes. While several members of this family are used in agriculture (e.g., as anti-coccidiostats) and have potent antibacterial activity, they are not currently being pursued as antibiotics for human use. Polyether ionophores are typically grouped as having similar functions, despite the fact that they significantly differ in structure; for this reason, how their structure and activity are related remains unclear. To determine whether certain members of the family constitute particularly interesting springboards for in-depth investigations and future synthetic optimization, we conducted a systematic comparative study of eight different polyether ionophores for their potential as antibiotics. This includes clinical isolates from bloodstream infections and studies of the compounds' effects on bacterial biofilms and persister cells. We uncover distinct differences within the compound class and identify the compounds lasalocid, calcimycin, and nanchangmycin as having particularly interesting activity profiles for further development. IMPORTANCE Polyether ionophores are complex natural products used in agriculture as anti-coccidiostats in poultry and as growth promoters in cattle, although their precise mechanism is not understood. They are widely regarded as antimicrobials against Gram-positive bacteria and protozoa, but fear of toxicity has so far prevented their use in humans. We show that ionophores generally have very different effects on Staphylococcus aureus, both in standard assays and in more complex systems such as bacterial biofilms and persister cell populations. This will allow us to focus on the most interesting compounds for future in-depth investigations and synthetic optimizations.


Asunto(s)
Antibacterianos , Antiinfecciosos , Humanos , Animales , Bovinos , Ionóforos/farmacología , Ionóforos/química , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Bacterias Grampositivas , Biopelículas , Pruebas de Sensibilidad Microbiana
9.
Br J Nurs ; 32(6): S4-S12, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36952372

RESUMEN

BACKGROUND: More than 90% of people with an ostomy worry about leakage, with associated high rates of psychological morbidity. AIMS: To assess the performance of a novel digital ostomy leakage notification system in subjects with faecal stomas who experience and worry about leakage. METHOD: A prospective, single-arm, pilot study (ClinicalTrials.gov: NCT04894084) with 25 subjects testing the product for 21 days. Subjects completed questionnaires at baseline and termination of study evaluating leakage episodes, leakage worry and quality of life (QoL). FINDINGS: Mean age was 56 years, 60% had an ileostomy, and 40% were females. Mean episodes of leakage outside the baseplate decreased significantly from 2.8 to 0.5 episodes after 21 days' use of the test product (P<0.001), worry about leakage decreased significantly (P<0.001) and QoL improved. CONCLUSION: The findings indicate strong improvements to emotional health with the test product, driven by reductions in leakage incidents outside baseplate and in users' worry about leakage.


Asunto(s)
Estomía , Estomas Quirúrgicos , Femenino , Humanos , Persona de Mediana Edad , Masculino , Calidad de Vida/psicología , Proyectos Piloto , Estudios Prospectivos , Estomía/psicología , Ileostomía , Encuestas y Cuestionarios
10.
Br J Nurs ; 32(1): 8-19, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36626266

RESUMEN

BACKGROUND: Leakage of stomal effluent outside the baseplate that soils clothes or bedsheets is a common problem for many people with a stoma and significantly impacts their quality of life. AIM: To understand behavioural changes for people experiencing faecal leakage outside the baseplate regarding the usage of pouching systems, supporting products and interactions with health professionals. METHODS: Retrospective, self-reported questionnaire. FINDINGS: Respondents on average experienced 1.1 incidents of faecal leakage outside the baseplate per fortnight. In periods with issues of leakage, 21% of respondents had been in contact with health professionals, 40% increased their use of pouching systems, 25% increased their use of existing supporting products, and 21% included additional supporting products to their change routine. The increased use of healthcare resources was estimated to cost £32.47 in the 3 weeks following a leakage incident. CONCLUSION: Incidents of leakage outside the baseplate lead to increased use of healthcare resources.


Asunto(s)
Calidad de Vida , Estomas Quirúrgicos , Humanos , Estudios Retrospectivos , Encuestas y Cuestionarios , Autoinforme
11.
J Autism Dev Disord ; 53(11): 4280-4292, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36001194

RESUMEN

It is unclear whether children with autism spectrum disorders have atypical semantic fluency and lower memory for the semantics of words. Therefore, we examined semantic typicality, fluency and recall for the categories of fruits and animals in 60 children with autism aged 7-15 years (boys: 48/girls: 12) compared to 60 typically developing controls. Relative to controls, the autism group had reduced animal fluency, fruit typicality and recall for fruits. Notably, these measures were associated with more autistic-like symptoms and/or lower adaptive functioning across the autism and control groups. In conclusion, atypical semantics of fruits in the autism group may reflect development of idiosyncratic semantic networks while their lower semantic fluency and recall suggest impaired executive language functions.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Masculino , Femenino , Humanos , Adolescente , Niño , Semántica , Lenguaje , Recuerdo Mental , Pruebas Neuropsicológicas
12.
Br J Nurs ; 31(16): S24-S38, 2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36094040

RESUMEN

BACKGROUND: People with a stoma are reported to experience leakage, which negatively impacts patient quality of life (QoL). AIM: To assess the impact of leakage experienced by individuals with a stoma in the UK. METHODS: Data were analysed from 301 patients living in the UK who completed a questionnaire concerning the physical and psychosocial impact of living with a stoma. FINDINGS: Most respondents had had their stoma for more than 5 years. Nine out of 10 worried about leakage to varying degrees and half the respondents accepted that this was a worry they had to live with. Almost 70% experienced leakage onto clothes within the preceding year, and 28% experienced this monthly. Peristomal skin complications were experienced by 82% of respondents, the severity of which correlated with reductions in QoL. CONCLUSION: Despite the consequential negative impact of leakage on QoL, individuals are not seeking advice to resolve leakage-related issues, including from their specialist stoma care nurse.


Asunto(s)
Calidad de Vida , Estomas Quirúrgicos , Humanos , Prevalencia , Estomas Quirúrgicos/efectos adversos , Encuestas y Cuestionarios , Reino Unido/epidemiología
13.
Front Psychol ; 13: 889245, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35814102

RESUMEN

We raise the new possibility that people diagnosed with developmental dyslexia (DD) are specialized in explorative cognitive search, and rather than having a neurocognitive disorder, play an essential role in human adaptation. Most DD research has studied educational difficulties, with theories framing differences in neurocognitive processes as deficits. However, people with DD are also often proposed to have certain strengths - particularly in realms like discovery, invention, and creativity - that deficit-centered theories cannot explain. We investigate whether these strengths reflect an underlying explorative specialization. We re-examine experimental studies in psychology and neuroscience using the framework of cognitive search, whereby many psychological processes involve a trade-off between exploration and exploitation. We report evidence of an explorative bias in DD-associated cognitive strategies. High DD prevalence and an attendant explorative bias across multiple areas of cognition suggest the existence of explorative specialization. An evolutionary perspective explains the combination of findings and challenges the view that individuals with DD have a disorder. In cooperating groups, individual specialization is favored when features that confer fitness benefits are functionally incompatible. Evidence for search specialization suggests that, as with some other social organisms, humans mediate the exploration-exploitation trade-off by specializing in complementary strategies. The existence of a system of collective cognitive search that emerges through collaboration would help to explain our species' exceptional adaptiveness. It also aligns with evidence for substantial variability during our evolutionary history and the notion that humans are adapted not to a particular habitat but to variability itself. Specialization creates interdependence and necessitates balancing complementary strategies. Reframing DD therefore underscores the urgency of changing certain cultural practices to ensure we do not inhibit adaptation. Key improvements would remove cultural barriers to exploration and nurture explorative learning in education, academia, and the workplace, as well as emphasize collaboration over competition. Specialization in complementary search abilities represents a meta-adaptation; through collaboration, this likely enables human groups (as a species and as cultural systems) to successfully adapt. Cultural change to support this system of collaborative search may therefore be essential in confronting the challenges humanity now faces.

14.
Autism Res ; 15(8): 1469-1481, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35545929

RESUMEN

Children and adolescents on the autism spectrum display sensory disturbances, rigid and repetitive behavior, social communication problems and a high prevalence of impaired adaptive functioning. Autism is associated with slowed behavioral and neural habituation to repeated sensory input and decreased responses to sensory deviations. Mismatch negativity (MMN) reflects a pre-attentive difference in the neural response to sensory deviations relative to regularities and studies overall suggest that children and adolescents with autism tend to have smaller MMN. However, it remains unclear whether reduced MMN in autism is coupled to severity of specific autistic symptoms or more generally to lower level of adaptive functioning. To address these questions, the present study used electroencephalography (EEG) to assess whether auditory MMN in 59 children and adolescents with autism aged 7-14 years compared to 59 typically developing children and adolescents were related to specific autistic symptoms or level in adaptive functioning. As hypothesized, the autism group had a lower MMN amplitude than controls. Smaller MMN amplitudes were specifically associated with lower adaptive functioning in the autistic subjects but not in controls while no apparent relationships were observed with autistic-like social interaction and communication problems, atypical language, rigidity, stereotypy or sensory sensitivity symptoms. Our findings indicate that a blunted response to changes in sensory input may underlie or contribute to the generalized difficulties with adapting to daily life circumstances seen in children and adolescents with autism. LAY SUMMARY: Children and adolescents on the autism spectrum have a high prevalence of impaired adaptive functioning. Neuroimaging studies have reported that children and adolescents with autism display attenuated brain activity when discriminating sensory input. However, it is unknown whether this attenuation is related to autistic symptoms and/or adaptive functioning. The present study used electroencephalogram (EEG) to show that attenuated brain response in discrimination of novel compared to repetitive sounds in children and adolescents with autism is related to their impaired adaptive functioning.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Estimulación Acústica/métodos , Adolescente , Trastorno del Espectro Autista/complicaciones , Encéfalo , Niño , Electroencefalografía/métodos , Humanos
15.
Br J Nurs ; 31(6): S48-S58, 2022 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-35333558

RESUMEN

BACKGROUND: Many people with a stoma experience leakage of stomal effluent. AIM: To investigate the impact of leakage on individuals with a stoma. METHODS: The Ostomy Life Study 2019 included a survey concerning experiences with stomal effluent leakage and the validated Ostomy Leak Impact tool. FINDINGS: Respondents with frequent leakage episodes were significantly more affected emotionally and they were feeling less in control than those who rarely or never experienced leakage. The emotional impact of experiencing leakage onto clothes appeared to last up to 1 year after the last leakage incidence. Because of worrying about leakage users increased their product usage and, of those who were in employment, 65% reported that leakage and the related worry influenced their ability to work. CONCLUSION: Most people with a stoma were emotionally impacted by experiencing leakage, especially by leakage outside the baseplate (resulting in soiled clothes). New solutions are warranted that can help reduce the impact of leakage.


Asunto(s)
Estomía , Estomas Quirúrgicos , Ansiedad , Humanos , Estomía/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios
17.
J Glob Antimicrob Resist ; 29: 29-41, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35131507

RESUMEN

The ATP synthase is a multicomponent enzyme that is largely conserved across the kingdoms of life. In many species the ATP synthase is central in the synthesis of ATP by using the electrochemical proton gradient generated via the electron transport chain. Bacteria inhabit very diverse ecological niches; hence their metabolism to extract nutrients and generation of ATP varies from species to species. Some species are obligate aerobes (e.g., Mycobacterium tuberculosis), relying on oxidative phosphorylation for ATP synthesis, whereas others are strict anaerobes (e.g., Clostridioides difficile) relying primarily on substrate-level phosphorylation using various fermentative pathways. Yet other species, such as Staphylococcus aureus and Escherichia coli are facultative anaerobes and can convert energy via both respiratory and fermentative pathways. The metabolic propensity and growth conditions experienced by bacterial species have a great impact on the necessity of a functional ATP synthase for viability. The ATP synthase has been validated as a druggable target with the approval of the ATP synthase inhibitor bedaquiline for treatment of M. tuberculosis, an organism in which the ATP synthase is essential for growth. Currently, no ATP synthase inhibitors are in clinical use against non-mycobacterial pathogens. In this review, the physiological functions of the ATP synthase in various bacterial pathogens are discussed in relation to the metabolic pathways utilized for providing energy. The ATP synthase is essential in important pathogenic species that are obligate aerobes, obligate anaerobes and aerotolerant anaerobes, whereas it is dispensable for growth in most facultative anaerobic pathogens. Interference with the ATP synthase in facultative anaerobes has physiological consequences, such as membrane hyperpolarization, which can be exploited for combination therapies. Collectively, the available data indicate that the ATP synthase is an interesting target for development of new antimicrobials beyond M. tuberculosis.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Adenosina Trifosfato/metabolismo , Inhibidores Enzimáticos/metabolismo , Humanos
18.
Microbiol Res ; 257: 126974, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35091344

RESUMEN

Emergence of antibiotic resistant bacteria is evolving at an alarming pace; therefore, we must start turning to alternative approaches. One of these, could be the use of antibiotic adjuvants that enhances the effect of antibiotics towards resistant bacteria. A novel antibiotic adjuvant is cannabidiol (CBD), which we have previously shown can enhance the effect of bacitracin (BAC). BAC targets cell wall synthesis by inhibiting dephosphorylation of the lipid carrier undecaprenyl pyrophosphate prior to recycling across the membrane. However, the mechanism underlying this CBD mediated potentiation of BAC has remained unknown. To explore this, we examined resistance to CBD in Staphylococcus aureus through daily exposures to CBD. By subsequent whole genome sequencing, we observed multiple genes to be mutated, including the farE/farR system encoding a fatty acid efflux pump (FarE) and its regulator (FarR). Importantly, recreation of mutations in these genes showed decreased susceptibility towards the combination of CBD and BAC. Furthermore, we searched the Nebraska Transposon Mutant Library for CBD susceptible strains and identified menH encoding a protein participating in menaquinone biosynthesis. Strains containing deletions in this and other menaquinone related genes showed increased susceptibility towards CBD, while addition of exogenous menaquinone reversed the effect and reduced susceptible towards CBD. These results suggest that CBD potentiates BAC by redirecting the isoprenoid precursor isopentenyl pyrophosphate towards production of menaquinone rather than the lipid carrier undecaprenyl pyrophosphate, which dephosphorylation is inhibited by BAC. This in turn might decrease the level of undecaprenyl pyrophosphate thus enhancing the effect of BAC. Our study illustrates how antibiotic adjuvants may apply to enhance efficacy of antimicrobial compounds.


Asunto(s)
Cannabidiol , Staphylococcus aureus , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Vitamina K 2
19.
Pediatr Res ; 91(4): 879-887, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-33790412

RESUMEN

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.


Asunto(s)
Síndrome Nefrótico , Sustancia Blanca , Adolescente , Anisotropía , Encéfalo , Niño , Imagen de Difusión Tensora/métodos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Síndrome Nefrótico/diagnóstico por imagen , Síndrome Nefrótico/tratamiento farmacológico , Fascículo Uncinado , Sustancia Blanca/diagnóstico por imagen
20.
Br J Nurs ; 30(22): S4-S12, 2021 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-34889680

RESUMEN

BACKGROUND: Leakage is a common problem for people with a stoma. AIM: To investigate how people with a stoma and stoma care nurses perceive different patterns of effluent under the baseplate. METHODS: The Ostomy Life Study 2019 included a user survey and a nurse survey covering experiences of leakage and the perception of leakage. FINDINGS: Most people with a stoma perceived effluent reaching outside the baseplate as leakage (88-90%), whereas effluent close to the stoma only was not perceived as leakage by the majority (81-91%). Effluent covering major parts of the baseplate was perceived as leakage by most respondents with a colostomy or ileostomy (83%), whereas fewer respondents with a urostomy perceived this as leakage (57%). Most of the nurses (70%) did not perceive effluent close to the stoma as leakage. CONCLUSION: This study revealed that effluent confined to the area next to the stoma is generally not perceived as leakage.


Asunto(s)
Estomía , Estomas Quirúrgicos , Colostomía , Humanos , Ileostomía , Percepción
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