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BACKGROUND: Medical Foundation Year (FY) doctors demonstrate greater psychological distress compared with the general population and other student groups. This feasibility study investigated FY doctors' perceptions of mindfulness and the impact of a mindful resilience and effectiveness training (MRET) programme on stress, wellbeing, and performance. METHODS: Mixed-methods study utilising a questionnaire (study 1, N = 144) and a pre-post analysis design of MRET programme (study 2, N = 13), along with focus groups (N = 7). RESULTS: In study 1 28.5% of FY's reported using mindfulness. All five mindfulness facets were significantly, and positively, associated with mental wellbeing (p < 0.05). Acting with awareness (AA) and non-reactivity (NR) were significantly, positively associated with a challenge responses to stress (p < 0.05). Threat and loss appraisals were negatively associated with AA, NR, and non-judging (p < 0.01). Perceived productivity was positively associated with mindfulness facets: describing, AA, and NR (p < 0.001). In study 2, there were significant increases in wellbeing and mindfulness facets observing, describing, AA, and NR, and threat appraisals decreased (p < 0.05). The main themes identified across the focus group included Reframed Mindset, Values-Based Action, Embodied Leadership and Pedagogy. CONCLUSIONS: There exists a relationship between mindfulness, psychological wellbeing, and performance in FYs. The MRET prorgamme improved psychological wellbeing and reduced threat appraisals. Future work could focus resources on enhancing the skills of AA and NR, as this may be sufficient to bring about meaningful improvements in wellbeing, percieved productivity and cognitive reappraisal of stressful life events.
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Estudos de Viabilidade , Atenção Plena , Resiliência Psicológica , Humanos , Masculino , Feminino , Adulto , Médicos/psicologia , Estresse Psicológico , Grupos Focais , Inquéritos e Questionários , Eficiência , Saúde MentalRESUMO
BACKGROUND: We examined whether the time to positivity (TTP) and growth and detection plot graph (GDPG) created by the automated blood culture system can be used to determine the bacterial load in bacteremic patients and its potential association correlation with disease severity. METHODS: Known bacterial inocula were injected into the blood culture bottles. The GDPGs for the specific inocula were downloaded and plotted. A cohort of 30 consecutive clinical cultures positive for S. aureus and E. coli was identified. Bacterial load was determined by comparing the GDPG with the "standard" curves. Variables associated with disease severity were compared across 3 bacterial load categories (< 100, 100-1000, > 1000 CFU/mL). RESULTS: S. aureus growth was sensitive to the blood volume obtained whereas E. coli growth was less so. A 12-hour delay in sample transfer to the microbiology laboratory resulted in a decrease in TTP by 2-3 h. Mean TTP was 15 and 10 h for S. aureus and E. coli, respectively, which correlates with > 1000 CFU/mL and 500-1000 CFU/ml. For S. aureus, patients with a bacterial load > 100 CFU/mL had a higher mortality rate, (OR for death = 9.7, 95% CI 1.6-59, p = 0.01). Bacterial load > 1000 CFU/mL had an odds ratio of 6.4 (95% CI1.2-35, p = 0.03) to predict an endovascular source. For E. coli bacteremia, we did not find any correlations with disease severity. CONCLUSION: GDPG retrieved from the automated blood culture system can be used to estimate bacterial load. S.aureus bacterial load, but not E.coli, was associated with clinical outcome.
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Histone proteins affect gene expression through multiple mechanisms, including through exchange with histone variants. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. Most notably, widely expressed variants of H2B remain elusive. We applied recently developed antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters, and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Further, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a mechanism linking histone variants to chromatin accessibility, transcriptional regulation, neuronal function, and memory. This work further identifies a widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.
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Cromatina , Histonas , Memória de Longo Prazo , Neurônios , Sinapses , Histonas/metabolismo , Histonas/genética , Animais , Cromatina/metabolismo , Cromatina/genética , Memória de Longo Prazo/fisiologia , Neurônios/metabolismo , Camundongos , Sinapses/metabolismo , Sinapses/genética , Regiões Promotoras Genéticas , Camundongos Endogâmicos C57BL , Regulação da Expressão Gênica , Transcrição Gênica , Masculino , HumanosRESUMO
Biological sex shapes the manifestation and progression of neurodevelopmental disorders (NDDs). These disorders often demonstrate male-specific vulnerabilities; however, the identification of underlying mechanisms remains a significant challenge in the field. Hemideletion of the 16p11.2 region (16p11.2 del/+) is associated with NDDs, and mice modeling 16p11.2 del/+ exhibit sex-specific striatum-related phenotypes relevant to NDDs. Striatal circuits, crucial for locomotor control, consist of two distinct pathways: the direct and indirect pathways originating from D1 dopamine receptor (D1R) and D2 dopamine receptor (D2R) expressing spiny projection neurons (SPNs), respectively. In this study, we define the impact of 16p11.2 del/+ on striatal circuits in male and female mice. Using snRNA-seq, we identify sex- and cell type-specific transcriptomic changes in the D1- and D2-SPNs of 16p11.2 del/+ mice, indicating distinct transcriptomic signatures in D1-SPNs and D2-SPNs in males and females, with a â¼5-fold greater impact in males. Further pathway analysis reveals differential gene expression changes in 16p11.2 del/+ male mice linked to synaptic plasticity in D1- and D2-SPNs and GABA signaling pathway changes in D1-SPNs. Consistent with our snRNA-seq study revealing changes in GABA signaling pathways, we observe distinct changes in miniature inhibitory postsynaptic currents (mIPSCs) in D1- and D2-SPNs from 16p11.2 del/+ male mice. Behaviorally, we utilize conditional genetic approaches to introduce the hemideletion selectively in either D1- or D2-SPNs and find that conditional hemideletion of genes in the 16p11.2 region in D2-SPNs causes hyperactivity in male mice, but hemideletion in D1-SPNs does not. Within the striatum, hemideletion of genes in D2-SPNs in the dorsal lateral striatum leads to hyperactivity in males, demonstrating the importance of this striatal region. Interestingly, conditional 16p11.2 del/+ within the cortex drives hyperactivity in both sexes. Our work reveals that a locus linked to NDDs acts in different striatal circuits, selectively impacting behavior in a sex- and cell type-specific manner, providing new insight into male vulnerability for NDDs. Highlights: - 16p11.2 hemideletion (16p11.2 del/+) induces sex- and cell type-specific transcriptomic signatures in spiny projection neurons (SPNs). - Transcriptomic changes in GABA signaling in D1-SPNs align with changes in inhibitory synapse function. - 16p11.2 del/+ in D2-SPNs causes hyperactivity in males but not females. - 16p11.2 del/+ in D2-SPNs in the dorsal lateral striatum drives hyperactivity in males. - 16p11.2 del/+ in cortex drives hyperactivity in both sexes.
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OBJECTIVES: Bacteroides fragilis is the most frequent cause of anaerobic bacteraemia. Although recent data suggest a rise in antimicrobial resistance (AMR) of this and other anaerobic bacteria, surveillance remains limited due to a lack of both data availability and comparability. However, a newly introduced standardised method for antimicrobial susceptibility testing (AST) of anaerobic bacteria has made larger scale surveillance possible for the first time. The aim of this study was to investigate phenotypic AMR of Bacteroides fragilis isolates from bacteraemia across Europe in 2022. METHODS: In a multicentre approach, clinical microbiology laboratories in Europe were invited to contribute results of AST for Bacteroides fragilis blood culture isolates (including only the first isolate per patient and year). AST of a selection of four antibiotics was performed locally by participating laboratories in a prospective or retrospective manner, using the new EUCAST disc diffusion method on fastidious anaerobe agar (FAA-HB). RESULTS: A total of 16 European countries reported antimicrobial susceptibilities in 449 unique isolates of Bacteroides fragilis from blood cultures in 2022. Clindamycin demonstrated the highest resistance rates (20.9%, range 0 - 63.6%), followed by piperacillin-tazobactam (11.1%, 0-54.5%), meropenem (13.4%, 0-45.5%), and metronidazole (1.8%, 0-20.0%), all with wide variation between countries. CONCLUSION: Considering that the mean resistance rates across Europe were higher than expected for three of the four anti-anaerobic antibiotics under surveillance, both local AST of clinically relevant isolates of Bacteroides fragilis and continued surveillance on an international level is warranted.
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Attachment relationships are widely recognized as influential in increasing prosocial tendencies, with existing literature indicating that human attachment can increase empathetic processes, thereby potentially facilitating prosocial behavior. Given that pets frequently fulfill the criteria for attachment figures, this study investigates whether the observed associations among human attachment, empathy, and prosocial attitudes extend to human-animal interactions (HAI). This study examines the relationship between pet attachment, animal empathy, and prosocial attitudes toward humans. The study hypothesizes that animal empathy mediates the association between pet attachment and prosocial attitudes. A cross-sectional survey was administered to 343 Filipino participants, predominantly consisting of single female young adults with college education backgrounds. Participants completed a battery of assessments including the Contemporary Companion Animal Bonding Scale (CCABS), the Animal Empathy Scale (AES), and the Prosocialness Scale for Adults (PSA). Aligned with our hypothesis, our study reveals that animal empathy plays a significant mediating role in the relationship between pet attachment and attitudes toward humans. We found that stronger pet attachment correlates positively with heightened animal empathy, subsequently leading to elevated levels of prosocial attitudes. Our findings prompt discussions on implications for understanding human-animal relationships and suggest avenues for future research exploration.
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Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories.1,2 Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD.3,4 However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown. The infralimbic cortex (IL) is a key brain structure for the consolidation of extinction memory.5 Using calcium imaging, we found in mice that most IL pyramidal neurons are intensively activated during REM sleep. Optogenetically suppressing the IL specifically during REM sleep within a 4-h window after auditory-cued fear conditioning impaired extinction memory consolidation. In contrast, REM-specific IL inhibition after extinction learning did not affect the extinction memory. Whole-cell patch-clamp recordings demonstrated that inactivating IL neurons during REM sleep depresses their excitability. Together, our findings suggest that REM sleep after fear conditioning facilitates fear extinction by enhancing IL excitability and highlight the importance of REM sleep in the aftermath of traumatic events for protecting against traumatic memories.
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Extinção Psicológica , Medo , Sono REM , Animais , Medo/fisiologia , Sono REM/fisiologia , Camundongos , Extinção Psicológica/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Memória/fisiologia , Consolidação da Memória/fisiologia , Condicionamento Clássico/fisiologia , Células Piramidais/fisiologiaRESUMO
Regulation of histone proteins affects gene expression through multiple mechanisms including exchange with histone variants. However, widely expressed variants of H2B remain elusive. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE, and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Lastly, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a novel mechanism linking histone variants to chromatin regulation, neuronal function, and memory. This work further identifies the first widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.
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Striatal dopamine governs a wide range of behavioral functions, yet local dopamine concentrations can be dissociated from somatic activity. Here, we discuss how dopamine's diverse roles in behavior may be driven by local circuit mechanisms shaping dopamine release. We first look at historical and recent work demonstrating that striatal circuits interact with dopaminergic terminals to either initiate the release of dopamine or modulate the release of dopamine initiated by spiking in midbrain dopamine neurons, with particular attention to GABAergic and cholinergic local circuit mechanisms. Then we discuss some of the first in vivo studies of acetylcholine-dopamine interactions in striatum and broadly discuss necessary future work in understanding the roles of midbrain versus striatal dopamine regulation.
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Corpo Estriado , Dopamina , Dopamina/fisiologia , Corpo Estriado/fisiologia , Acetilcolina , Neurônios Dopaminérgicos/fisiologiaRESUMO
Defense and Security Personnel (DSP) often have to operate in the presence of stressful demands. Prior research has identified factors and processes associated with DSP being able to perform resiliently in demanding situations and settings. The aim of the present study was to develop a resilient performance training programme for UK defense and security operators. An intervention mapping (IM) method was used to guide the development of the programme. Typically, IM follows six sequential phases. In the present work, these phases were shaped by insights from prior research (e.g. systematic review and end user interviews), the input of a dedicated working group (N = 13) and from practitioner focus groups. During the IM process, the importance of programme flexibility was emphasized by practitioners. As such, the enAbling REsilieNt performAnce (ARENA) training programme was designed to be agile and include both face-to-face training and online learning modules. Theoretical behavior change principles, closely aligned to findings of earlier work on resilient defense and security performance, were used to underpin programme content and delivery. Future research should seek to gather data on the impact of the ARENA programme, in the targeted biological, psychological and social factors that previously been associated with resilient performances.
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OBJECTIVE: The development of serious games for mental wellbeing is a topic of growing interest. The increase in acceptance of games as a mainstream entertainment medium combined with the immersive qualities of games provides opportunities for meaningful support and intervention in mental wellbeing. METHOD: We conducted a systematic review and exploratory meta-analysis to examine if aspects of the interventions influenced outcomes as measured via overall effect sizes. We employed a multilevel meta-analytic approach to accommodate the interdependency of effect sizes (18 effect sizes from 14 studies, with 2027 participants). RESULTS: Overall, the main effect for gaming interventions on any outcome variable was small to medium sized, d = .35 (confidence interval [.23, 47], p < .001). Results revealed that the only significant moderator was the nature of the intervention. Specifically, only interventions that included a rational emotional behavioural focus significantly predicted an improvement in depression and/or anxiety in participants. CONCLUSION: The findings reveal promising effects for therapeutic games for mental health, but replications are needed, alongside the addressing of methodological and procedural concerns.
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The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target.
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Ínsulas Olfatórias , Estriado Ventral , Camundongos , Animais , Depressão , Tubérculo Olfatório , Neurônios DopaminérgicosRESUMO
To successfully complete a Polar expedition individuals and teams must respond resiliently to the environmental, psychological, and social demands they face. In this study we examined profiles of resilient function in seven people from three expeditions in the High Arctic. Using a structured daily diary, participants reported on experiences of physical health (morning and evening), affect, team cohesion, performance, and potential explanatory factors including sleep, demand appraisals, events, and coping strategies. Notable intra- and inter-individual variability was observed in daily reports and all profiles could be interpreted as representing resilient function. A number of significant relationships were found between markers of resilient physical and psychosocial function and potential explanatory variables. For example, there was much more daily variability in an individual's reporting of positive affect than prior research might imply, and what prior research designs could capture. Further, while negative affect tended to remain low and stable, our findings reveal that even minor and infrequent increases in negative emotions were significantly associated with other variables in the network. Finally, across the expedition period individual coping resources consistently exceeded demands, suggesting that individuals viewed the expedition as a challenge and not a threat. More broadly, these findings inform efforts to monitor, and maintain resilience when operating in Polar and other extreme settings.
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BACKGROUND: Antimicrobial resistance is common in Nocardia species but data regarding the molecular mechanisms beyond their resistance traits are limited. Our study aimed to determine the species distribution, the antimicrobial susceptibility profiles, and investigate the associations between the resistance traits and their genotypic determinants. METHODS: The study included 138 clinical strains of Nocardia from nine Israeli microbiology laboratories. MIC values of 12 antimicrobial agents were determined using broth microdilution. WGS was performed on 129 isolates of the eight predominant species. Bioinformatic analysis included phylogeny and determination of antimicrobial resistance genes and mutations. RESULTS: Among the isolates, Nocardia cyriacigeorgica was the most common species (36%), followed by Nocardia farcinica (16%), Nocardia wallacei (13%), Nocardia abscessus (9%) and Nocardia brasiliensis (8%). Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%). Resistance to other antibiotics was species-specific, often associated with the presence of resistance genes or mutations: (1) aph(2â³) in N. farcinica and N. wallacei (resistance to tobramycin); (ii) blaAST-1 in N. cyriacigeorgica and Nocardia neocaledoniensis (resistance to amoxicillin/clavulanate); (iii) blaFAR-1 in N. farcinica (resistance to ceftriaxone); (iv) Ser83Ala substitution in the gyrA gene in four species (resistance to ciprofloxacin); and (v) the 16S rRNA m1A1408 methyltransferase in N. wallacei isolates (correlating with amikacin resistance). CONCLUSIONS: Our study provides a comprehensive understanding of Nocardia species diversity, antibiotic resistance patterns, and the molecular basis of antimicrobial resistance. Resistance appears to follow species-related patterns, suggesting a lesser role for de novo evolution or transmission of antimicrobial resistance.
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Anti-Infecciosos , Nocardiose , Nocardia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amicacina , RNA Ribossômico 16S/genética , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genética , Nocardia/genética , Anti-Infecciosos/farmacologiaRESUMO
BACKGROUND: NDM-producing Acinetobacter baumannii (NDMAb) were reported sporadically worldwide but little is known about the transmission, epidemiology and clinical features of NDMAb-infected patients. The goals of this study were to characterize (1) the epidemiology and clinical features of NDMAb-infected patients; (2) the microbiological and molecular features of NDMAb isolates and (3) the transmission networks of NDMAb within healthcare facilities. METHODS: The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical centers (TASMC, RMC and SZMC, respectively) in Israel. All cases detected between January 2018 and July 2019 were included. Phylogenetic analysis was based on core genome SNP distances. Clonal transmission was defined according to molecular (≤ 5 SNP) and epidemiological criteria (overlapping hospital stay). NDMAb cases were compared at a ratio of 1:2 with non-NDM carbapenem-resistant A. baumannii (CRAb) cases. RESULTS: The study included 54 NDMAb-positive out of 857 CRAb patients, including 6/179 (3.3%) in TASMC, 18/441 (4.0%) in SZMC and 30/237 (12.6%) in RMC. Patients infected by NDMAb had similar clinical features and risk factors as patients with non-NDM CRAb. The length-of-stay was higher in NDMAb cases (48.5 days vs. 36 days, respectively, p = 0.097) and the in-hospital mortality was similarly high in both groups. Most isolates (41/54, 76%) were first detected from surveillance culture. The majority of isolates harbored the blaNDM-2 gene allele (n = 33), followed by the blaNDM-1 (n = 20) allele and the blaNDM-4 allele (n = 1). The majority of isolates were related within the ST level to other isolates in SZMC and RMC: 17/18 and 27/30 isolates, respectfully. The common ST's were the blaNDM-1 harboring ST-2 (n = 3) and ST-107 (n = 8) in SZMC and the blaNDM-2 harboring ST-103 in SZMC (n = 6) and in RMC (n = 27). All blaNDM alleles were located within a conserved mobile genetic environment flanked by the ISAb125 and IS91 family transposon. Clonal transmission was identified in most hospital-acquired cases in RMC and SZMC. CONCLUSION: NDMAb constitutes a minor part of CRAb cases and are clinically similar to non-NDM CRAb. Transmission of NDMAb occurs mostly by clonal spread.
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Acinetobacter baumannii , Humanos , Israel/epidemiologia , Acinetobacter baumannii/genética , Filogenia , Alelos , Carbapenêmicos/farmacologiaRESUMO
OBJECTIVE: Taking regular rest breaks while working positively impacts productivity and wellbeing. While home and hybrid working styles have become a popular choice for employees, the impact of, and perceptions towards, taking breaks while working at home is poorly understood. The current research aimed to explore attitudes towards taking rest breaks while working from home and capture levels of breaks taken, wellbeing and productivity in a sample of UK white-collar workers. METHODS: A mixed method approach was applied where self-report data from an online survey were gathered from individuals (N = 140) from one organisation. Open-ended questions regarding attitudes and perceptions towards rest break behaviours were obtained. Further quantitative measures included the number of breaks taken while working from home, levels of productivity (measured by the Health and performance Presenteeism subscale) and mental wellbeing (measured by the Short Warwick-Edinburgh Mental wellbeing scale). Both quantitative and qualitative analysis approaches were applied. RESULTS: Qualitative responses indicated two overarching themes (1) Personal and (2) Organisational sat above four further themes including Movement outside, Structure of home working, Home environment and Digital presence. Additionally, quantitative findings indicated that the number of breaks taken outside was associated with positive changes in wellbeing. CONCLUSION: Employers could aim to support employees working from home in taking outside breaks through flexible working patterns, authentic leadership, and a change in company social norms around break behaviours. Such organisational changes could help to improve workforce productivity and wellbeing.
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Atitude , Humanos , Inquéritos e Questionários , AutorrelatoRESUMO
As a result of the increasing use of sensitive nucleic acid amplification tests, Kingella kingae is being recognized as a common pathogen of early childhood, causing medical conditions ranging from asymptomatic oropharyngeal colonization to bacteremia, osteoarthritis, and life-threatening endocarditis. However, the genomic determinants associated with the different clinical outcomes are unknown. Employing whole-genome sequencing, we studied 125 international K. kingae isolates derived from 23 healthy carriers and 102 patients with invasive infections, including bacteremia (n = 23), osteoarthritis (n = 61), and endocarditis (n = 18). We compared their genomic structures and contents to identify genomic determinants associated with the different clinical conditions. The mean genome size of the strains was 2,024,228 bp, and the pangenome comprised 4,026 predicted genes, of which 1,460 (36.3%) were core genes shared by >99% of the isolates. No single gene discriminated between carried and invasive strains; however, 43 genes were significantly more frequent in invasive isolates, compared to asymptomatically carried organisms, and a few showed a significant differential distribution among isolates from skeletal system infections, bacteremia, and endocarditis. The gene encoding the iron-regulated protein FrpC was uniformly absent in all 18 endocarditis-associated strains but was present in one-third of other invasive isolates. Similar to other members of the Neisseriaceae family, the K. kingae differences in invasiveness and tropism for specific body tissues appear to depend on combinations of multiple virulence-associated determinants that are widely distributed throughout the genome. The potential role of the absence of the FrpC protein in the pathogenesis of endocardial invasion deserves further investigation. IMPORTANCE The wide range of clinical severities exhibited by invasive Kingella kingae infections strongly suggests that isolates differ in their genomic contents, and strains associated with life-threatening endocarditis may harbor distinct genomic determinants that result in cardiac tropism and severe tissue damage. The results of the present study show that no single gene discriminated between asymptomatically carried isolates and invasive strains. However, 43 putative genes were significantly more frequent among invasive isolates than among pharyngeal colonizers. In addition, several genes displayed a significant differential distribution among isolates from bacteremia, skeletal system infections, and endocarditis, suggesting that the virulence and tissue tropism of K. kingae are multifactorial and polygenic, depending on changes in the allele content and genomic organization. Further analysis of these putative genes may identify genomic determinants of the invasiveness of K. kingae and its affinity for specific body tissues and potential targets for a future protective vaccine.
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Bacteriemia , Endocardite , Kingella kingae , Humanos , Pré-Escolar , Kingella kingae/genética , Virulência/genética , Fatores de Virulência/genética , Bacteriemia/patologiaRESUMO
Fronto-striatal circuits have been implicated in cognitive control of behavioral output for social and appetitive rewards. The functional diversity of prefrontal cortical populations is strongly dependent on their synaptic targets, with control of motor output mediated by connectivity to dorsal striatum. Despite evidence for functional diversity along the anterior-posterior striatal axis, it is unclear how distinct fronto-striatal sub-circuits support value-based choice. Here we found segregated prefrontal populations defined by anterior/posterior dorsomedial striatal target. During a feedback-based 2-alternative choice task, single-photon imaging revealed circuit-specific representations of task-relevant information with prelimbic neurons targeting anterior DMS (PL::A-DMS) robustly modulated during choices and negative outcomes, while prelimbic neurons targeting posterior DMS (PL::P-DMS) encoded internal representations of value and positive outcomes contingent on prior choice. Consistent with this distributed coding, optogenetic inhibition of PL::A-DMS circuits strongly impacted choice monitoring and responses to negative outcomes while inhibition of PL::P-DMS impaired task engagement and strategies following positive outcomes. Together our data uncover PL populations engaged in distributed processing for value-based choice.
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Corpo Estriado , Neostriado , Camundongos , Masculino , Animais , Corpo Estriado/fisiologia , Córtex Pré-Frontal/fisiologia , Inibição PsicológicaRESUMO
BACKGROUND: Blood culture contamination is associated with health care costs and potential patient harm. Diversion of the initial blood specimen reduces blood culture contamination. We report results of the "real-life" clinical implementation of this technique. METHODS: Following an educational campaign, use of a dedicated diversion tube was recommended prior to all blood cultures. Blood culture sets taken from adults using a diversion tube were defined as "diversion sets," those without, "non-diversion" sets. Blood culture contamination and true positive rates were compared for diversion and nondiversion sets and to nondiversion historical controls. A secondary analysis investigated efficacy of diversion by patient age. RESULTS: Out of 20,107 blood culture sets drawn, the diversion group included 12,774 (60.5%) and the nondiversion group 8,333 (39.5%) sets. The historical control group included 32,472 sets. Comparing nondiversion to diversion, contamination decreased by 31% (5.5% [461/8333] to 3.8% [489/12744], P < .0001]. Contamination was also 12% lower in diversion than historical controls [3.8% (489/12744) vs 4.3% (1,396/33,174) P = .02)]. The rate of true bacteremia was similar. In older patients, contamination rate was higher, and the relative reduction associated with diversion decreased (54.3% amongst 20-40-year-olds vs 14.5% amongst >80-year-olds). CONCLUSIONS: Use of a diversion tube in the ED reduced blood culture contamination in this large real life observational study. Efficacy decreased with increasing age, which requires further investigation.
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Bacteriemia , Coleta de Amostras Sanguíneas , Adulto , Humanos , Idoso , Hemocultura/métodos , Melhoria de Qualidade , Bacteriemia/prevenção & controle , Custos de Cuidados de Saúde , Contaminação de EquipamentosRESUMO
BACKGROUND: To promote the rational use of cardiovascular imaging in patients with congenital heart disease, the American College of Cardiology developed Appropriate Use Criteria (AUC), but its clinical application and pre-release benchmarks have not been evaluated. We aimed to evaluate the appropriateness of indications for cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) in patients with conotruncal defects and to identify factors associated with maybe or rarely appropriate (M/R) indications. METHODS: Twelve centers each contributed a median of 147 studies performed prior to AUC publication (01/2020) on patients with conotruncal defects. To incorporate patient characteristics and center-level effects, a hierarchical generalized linear mixed model was used. RESULTS: Of the 1753 studies (80% CMR, and 20% CCT), 16% were rated M/R. Center M/R ranged from 4 to 39%. Infants accounted for 8.4% of studies. In multivariable analyses, patient- and study-level factors associated with M/R rating included: age <1 year (OR 1.90 [1.15-3.13]), truncus arteriosus (vs. tetralogy of Fallot, OR 2.55 [1.5-4.35]), and CCT (vs. CMR, OR 2.67 [1.87-3.83]). None of the provider- or center-level factors reached statistical significance in the multivariable model. CONCLUSIONS: Most CMRs and CCTs ordered for the follow-up care of patients with conotruncal defects were rated appropriate. However, there was significant center-level variation in appropriateness ratings. Younger age, CCT, and truncus arteriosus were independently associated with higher odds of M/R rating. These findings could inform future quality improvement initiatives and further exploration of factors resulting in center-level variation.