The role of illness perceptions in delayed care-seeking in heart failure: A mixed-methods study.

BACKGROUND: Unclear illness perceptions are common in heart failure. The self-regulation model of illness behaviour highlights factors that may impact how people with chronic illness choose to cope with or manage their condition and has been used to study pre-hospital delay for stroke and acute myocardial infarction. The principles of self-regulation can be applied in heart failure to help illuminate the link between unclear illness perceptions and sub-optimal symptom self-management. OBJECTIVE: Informed by the self-regulation model of illness behaviour, this study examines the role of illness perceptions in coping responses that lead to delayed care-seeking for heart failure symptoms. DESIGN: Mixed-methods phenomenological study. SETTING(S): Quaternary referral hospital - centre of excellence for cardiovascular care and heart transplantation. PARTICIPANTS: Seventy-two symptomatic patients with heart failure participated in a survey assessing illness perceptions. A subset of fifteen individuals was invited to participate in semi-structured interviews. METHODS: Illness perceptions were assessed using the Brief Illness Perception Questionnaire. In-depth semi-structured interviews were conducted to elicit previous care-seeking experiences and decision-making that led to a passive, or active coping response to worsening symptoms. Descriptive statistics were used to report questionnaire findings, and open-ended responses were grouped into descriptive categories. Interpretative phenomenological analysis was undertaken on interview transcripts. RESULTS: Participants perceived little personal control over their condition and mostly attributed heart failure to lifestyle factors such as diet and lack of activity. Cognitive dissonance between perceived self-identity and heart failure-identity led to a highly emotional response which drove coping towards avoidance strategies and denial. CONCLUSIONS: This study demonstrates the use of the principles of self-regulation in heart failure and offers a framework to understand how patient representations and emotional responses can inform behaviour in illness. Findings highlight the value of empowering patients to take control of their health and the need to help align values (e.g. independence) with behaviours (e.g. actively addressing problems) to facilitate optimal symptom self-management.

The Patient Experience After Spontaneous Coronary Artery Dissection.

OBJECTIVE: There is considerable burden of anxiety, depression, and post-traumatic stress disorder in patients with spontaneous coronary artery dissection (SCAD), yet research is limited on the experience and impact of SCAD from the patient perspective. This literature review sought to describe the current state of the literature on the patient experience of SCAD and consequences for patients following a SCAD event from the patient perspective. To better understand how people's experiences of SCAD affect their wellbeing, quality of life, lifestyles, and identity, and what would be useful from the patient perspective, an integrative review was performed. METHODS: An integrative literature review was conducted to understand the experience of SCAD and the post-event implications. Five databases were searched. Search terms included 'spontaneous coronary artery dissection', 'SCAD', 'patient', 'experience', 'perspective', and 'opinion'. English-language, peer-reviewed primary research in people with a diagnosis of SCAD that reflected the patient experience was included. Data indicating the SCAD experience including distress prevalence were extracted into an Excel spreadsheet, and narrative synthesis of included studies followed. FINDINGS: From 325 identified studies, five were included for review, yielding a combined sample of 447 participants. Patients with SCAD reported a lack of information about SCAD and the recovery process, and use of the internet for obtaining information. Patients with SCAD reported challenges in recovery including anxiety associated with fear of recurrence and uncertainty, and a need for greater support. A wide range of negative emotions was reported during and after the SCAD event. Participants reported participating in support groups, with mixed reviews of their appropriateness and effectiveness.

Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis.

Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is 'at-risk' for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA. Tetramer studies show increased abundance of T cells recognizing citrullinated (cit) epitopes in At-Risk participants, including expansion of T cells reactive to citrullinated cartilage intermediate layer protein I (cit-CILP); these T cells have Th1, Th17, and T stem cell memory-like phenotypes. Antibody-antigen array analyses show that antibodies targeting cit-clusterin, cit-fibrinogen and cit-histone H4 are elevated in At-Risk and Early RA participants, with the highest levels of antibodies detected in those with Early RA. These findings indicate that an ACPA positive at-risk state is associated with multifaceted immune dysregulation that may represent a potential opportunity for targeted intervention.

Hippocampal mechanisms resolve competition in memory and perception.

Behaving adaptively requires selection of relevant memories and sensations and suppression of competing ones. We hypothesized that these mechanisms are linked, such that hippocampal computations that resolve competition in memory also shape the precision of sensory representations to guide selective attention. We leveraged f MRI-based pattern similarity, receptive field modeling, and eye tracking to test this hypothesis in humans performing a memory-dependent visual search task. In the hippocampus, differentiation of competing memories predicted the precision of memory-guided eye movements. In visual cortex, preparatory coding of remembered target locations predicted search successes, whereas preparatory coding of competing locations predicted search failures due to interference. These effects were linked: stronger hippocampal memory differentiation was associated with lower competitor activation in visual cortex, yielding more precise preparatory representations. These results demonstrate a role for memory differentiation in shaping the precision of sensory representations, highlighting links between mechanisms that overcome competition in memory and perception.

Hospital-service use in the last year of life by patients aged ⩾60 years who died of heart failure or cardiomyopathy: A retrospective linked data study.

BACKGROUND: Understanding patterns of health care use in the last year of life is critical in health services planning. AIM: To describe hospital-based service and palliative care use in hospital in the year preceding death for patients who died of heart failure or cardiomyopathy in Queensland from 2008 to 2018 and had at least one hospitalisation in the year preceding death. DESIGN: A retrospective data linkage study was conducted using administrative health data relating to hospitalisations, emergency department visits and deaths. PARTICIPANTS AND SETTING: Participants included were those aged ⩾60 years, had a hospitalisation in their last year of life and died of heart failure or cardiomyopathy in Queensland, Australia. RESULTS: Of the 4697 participants, there were 25,583 hospital admissions. Three quarters (n = 3420, 73%) of participants were aged ⩾80 years and over half died in hospital (n = 2886, 61%). The median number of hospital admissions in the last year of life was 3 (interquartile range [IQR] 2-5). The care type was recorded as 'acute' for 89% (n = 22,729) of hospital admissions, and few (n = 853, 3%) hospital admissions had a care type recorded as 'palliative.' Of the 4697 participants, 3458 had emergency department visit(s), presenting 10,330 times collectively. CONCLUSION: In this study, patients who died of heart failure or cardiomyopathy were predominantly aged ⩾80 years and over half died in hospital. These patients experienced repeat acute hospitalisations in the year preceding death. Improving timely access to palliative care services in the outpatient or community setting is needed for patients with heart failure.

Structural effects on custom, flexible iris prostheses passing through injector systems.

PURPOSE: To determine the suitability of various commercially available intraocular lens injection systems for the implantation of custom, flexible artificial irides of various sizes, both with and without fiber meshwork. SETTING: Cincinnati Eye Institute, Blue Ash, Ohio. DESIGN: Laboratory study. METHODS: Custom, flexible iris prostheses, both with and without fiber meshwork, were either maintained at a 12.8 mm diameter or trephinated to a 10 mm diameter and subsequently inserted through 7 different intraocular lens injector systems. The ease of load, difficulty of injection, control of injection, and level of prosthetic distortion, if any, were observed and recorded. RESULTS: The fiber-free devices universally passed through the injectors unaffected. Each of the iris prostheses with embedded fiber meshwork appeared grossly distorted after injection. The injection systems had differing amounts of effort to load the device into the cartridge, to advance the prosthetic through the system, and varying levels of control when the prosthetic was released, although all the systems delivered the device effectively. CONCLUSIONS: Any of the 7 injection systems tested in this study can be used effectively for fiber-free artificial irides. Caution should be taken to ensure that control of insertion is maintained throughout the injection process. Screw-type injectors required less effort and yielded more control than plunger-type injector. Fiber meshwork-containing artificial irides should not be inserted through an injector.

Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis.

Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs), implicating oral mucosal inflammation in RA pathogenesis. Here, we performed paired analysis of human and bacterial transcriptomics in longitudinal blood samples from RA patients. We found that patients with RA and periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of ISG15+HLADRhi and CD48highS100A2pos monocytes, recently identified in inflamed RA synovia and blood of those with RA flares. The oral bacteria observed transiently in blood were broadly citrullinated in the mouth, and their in situ citrullinated epitopes were targeted by extensively somatically hypermutated ACPAs encoded by RA blood plasmablasts. Together, these results suggest that (i) periodontal disease results in repeated breaches of the oral mucosa that release citrullinated oral bacteria into circulation, which (ii) activate inflammatory monocyte subsets that are observed in inflamed RA synovia and blood of RA patients with flares and (iii) activate ACPA B cells, thereby promoting affinity maturation and epitope spreading to citrullinated human antigens.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain / Características de los pacientes, patrones de tratamiento, uso de recursos y costes en adultos con dermatitis atópica moderada-grave en la práctica habitual en España: Estudio Derma-Atopic

Background Moderate–severe atopic dermatitis (AD) has a significant impact on patients’ lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. Methods This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. Results Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. Conclusions Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD (AU)

Antecedentes La dermatitis atópica (DA) moderada-grave tiene un impacto significativo en la vida de los pacientes, muchos de los cuales requieren tratamiento sistémico para controlar los síntomas (p. ej., prurito). Algunos tratamientos son usados fuera de indicación. Este estudio describió características sociodemográficas y clínicas, patrones de tratamiento, uso de recursos sanitarios (URS) y costes asociados en adultos con DA que iniciaron tratamiento sistémico o fototerapia en la práctica habitual. Métodos Este estudio observacional retrospectivo de historias clínicas electrónicas en la base de datos BIG-PAC identificó adultos con diagnóstico previo de DA (CIE-9: 691.8 o 692.9) que comenzaron con corticosteroides orales, inmunosupresores, biológicos o fototerapia entre el 01/01/2012 y el 31/12/2016. Se siguió a los pacientes durante 3 años desde el inicio del tratamiento, hasta 31/12/2019. Los datos sobre las características clínicas de los pacientes, patrones de tratamiento, URS y costes se analizaron de forma descriptiva. Resultados Los pacientes (N = 1995) tenían una edad media de 60 años, el 64% eran mujeres, con una media de 23 años desde el diagnóstico (84% tenían ≥ 18 años al inicio de la DA). Las principales comorbilidades fueron ansiedad (38%), hipertensión arterial (36%) y dislipidemia (35%). La mayoría de los pacientes utilizaron corticosteroides orales como primer tratamiento sistémico (84%; duración media 29 días) e inmunosupresores en el 13% de los pacientes (duración media 117 días, ciclosporina en el 5% y metotrexato en el 4%). La mitad de los pacientes requirieron una segunda línea de tratamiento sistémico y el 12% una tercera. El uso de inmunosupresores y biológicos aumentó simultáneamente con las líneas de tratamiento. Aproximadamente el 13% de los pacientes recibieron tratamientos sistémicos de forma continua durante los 3 años de seguimiento. El coste medio por paciente a 3 años fue de 3.835 euros, con un coste medio anual de 1.278 euros (AU)

[Artículo traducido] Características de los pacientes, patrones de tratamiento, uso de recursos y costes en adultos con dermatitis atópica moderada-grave en la práctica habitual en España: Estudio Derma-Atopic / Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain

Antecedentes La dermatitis atópica (DA) moderada-grave tiene un impacto significativo en la vida de los pacientes, muchos de los cuales requieren tratamiento sistémico para controlar los síntomas (p. ej., prurito). Algunos tratamientos son usados fuera de indicación. Este estudio describió características sociodemográficas y clínicas, patrones de tratamiento, uso de recursos sanitarios (URS) y costes asociados en adultos con DA que iniciaron tratamiento sistémico o fototerapia en la práctica habitual. Métodos Este estudio observacional retrospectivo de historias clínicas electrónicas en la base de datos BIG-PAC identificó adultos con diagnóstico previo de DA (CIE-9: 691.8 o 692.9) que comenzaron con corticosteroides orales, inmunosupresores, biológicos o fototerapia entre el 01/01/2012 y el 31/12/2016. Se siguió a los pacientes durante 3 años desde el inicio del tratamiento, hasta 31/12/2019. Los datos sobre las características clínicas de los pacientes, patrones de tratamiento, URS y costes se analizaron de forma descriptiva. Resultados Los pacientes (N = 1995) tenían una edad media de 60 años, el 64% eran mujeres, con una media de 23 años desde el diagnóstico (84% tenían ≥ 18 años al inicio de la DA). Las principales comorbilidades fueron ansiedad (38%), hipertensión arterial (36%) y dislipidemia (35%). La mayoría de los pacientes utilizaron corticosteroides orales como primer tratamiento sistémico (84%; duración media 29 días) e inmunosupresores en el 13% de los pacientes (duración media 117 días, ciclosporina en el 5% y metotrexato en el 4%). La mitad de los pacientes requirieron una segunda línea de tratamiento sistémico y el 12% una tercera. El uso de inmunosupresores y biológicos aumentó simultáneamente con las líneas de tratamiento. Aproximadamente el 13% de los pacientes recibieron tratamientos sistémicos de forma continua durante los 3 años de seguimiento. El coste medio por paciente a 3 años fue de 3.835 euros, con un coste medio anual de 1.278 euros (AU)

Background Moderate–severe atopic dermatitis (AD) has a significant impact on patients’ lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. Methods This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. Results Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. Conclusions Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD (AU)

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N=1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain. / [Artículo traducido] Características de los pacientes, patrones de tratamiento, uso de recursos y costes en adultos con dermatitis atópica moderada-grave en la práctica habitual en España: Estudio Derma-Atopic.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Perception and memory have distinct spatial tuning properties in human visual cortex.

Reactivation of earlier perceptual activity is thought to underlie long-term memory recall. Despite evidence for this view, it is unclear whether mnemonic activity exhibits the same tuning properties as feedforward perceptual activity. Here, we leverage population receptive field models to parameterize fMRI activity in human visual cortex during spatial memory retrieval. Though retinotopic organization is present during both perception and memory, large systematic differences in tuning are also evident. Whereas there is a three-fold decline in spatial precision from early to late visual areas during perception, this pattern is not observed during memory retrieval. This difference cannot be explained by reduced signal-to-noise or poor performance on memory trials. Instead, by simulating top-down activity in a network model of cortex, we demonstrate that this property is well explained by the hierarchical structure of the visual system. Together, modeling and empirical results suggest that computational constraints imposed by visual system architecture limit the fidelity of memory reactivation in sensory cortex.

Phlebotominae Fauna (Diptera: Psychodidae) and Molecular Detection of Leishmania (Kinetoplastida: Trypanosomatidae) in Urban Caves of Belo Horizonte, Minas Gerais, Brazil.

Sand flies are often collected in urban areas, which has several implications for the risk of transmission of Leishmania Ross, 1903, to humans and other mammals. Given this scenario, we describe the sand fly fauna of caves and their surroundings in Mangabeiras Municipal Park (MMP) and Paredão Serra do Curral Park (PSCP), both located in the urban area of Belo Horizonte, Minas Gerais, Brazil, an endemic focus of visceral and cutaneous leishmaniasis. Collections were conducted monthly from November 2011 to October 2012, using CDC light traps exposed for two consecutive nights in four caves and their surroundings. Nonsystematized collections using Shannon traps and active searches were also performed around the caves. The presence of Leishmania DNA in collected female sand flies was evaluated by ITS1-PCR. A total of 857 sand flies representing fourteen species were collected in MMP, of which Evandromyia edwardsi (Mangabeira, 1941) was the most abundant. Leishmania amazonensis was detected in Brumptomyia nitzulescui (Costa Lima, 1932) and Ev. edwardsi, with the latter also having Leishmania braziliensis, Leishmania infantum, and Leishmania sp. A total of 228 sand flies representing four species were collected in PSCP, of which Sciopemyia microps (Mangabeira, 1942) was the most abundant. No females from PSCP were positive for Leishmania-DNA. Studies aimed at describing sand fly faunas of cave environments and detecting Leishmania are essential to understanding the relationship between these insects and this ecotope and assessing and monitoring areas that may pose risks to the health of visitors and employees.

Elements of Integrated Palliative Care in Chronic Heart Failure Across the Care Continuum: A Scoping Review.

BACKGROUND: Individuals with chronic heart failure experience high symptom burden, reduced quality of life and high health care utilisation. Although there is growing evidence that a palliative approach, provided concurrently with usual treatment improves outcomes, the method of integrating palliative care for individuals living with chronic heart failure across the care continuum remains elusive. AIM: To examine the key elements of integrated palliative care recommended for individuals living with chronic heart failure across the care continuum. DESIGN: Scoping review. DATA SOURCES: Databases searched were CINAHL, Ovid MEDLINE, Scopus and OpenGrey. Studies written in English and containing key strategic elements specific to chronic heart failure were included. Search terms relating to palliative care and chronic heart failure and the Joanna Briggs Institute methodology for scoping reviews was used. RESULTS: Seventy-nine (79) articles were selected that described key elements to integrate palliative care for individuals with chronic heart failure. This review identifies four levels of key strategic elements: 1) clinical; 2) professional; 3) organisational and 4) system-level integration. Implementing strategies across these elements facilitates integrated palliative care for individuals with chronic heart failure. CONCLUSIONS: Inter-sectorial collaborations across systems and the intersection of health and social services are essential to delivering integrated, person-centred palliative care. Further research focussing on patient and family needs at a system-level is needed. Research with strong theoretical underpinnings utilising implementation science methods are required to achieve and sustain complex behaviour change to translate key elements.

Abrupt hippocampal remapping signals resolution of memory interference.

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. We tested this idea using high-resolution, pattern-based fMRI analyses. Here we show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. The magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide insight into why remapping occurs.

A report on the impact of rapid prenatal exome sequencing on the clinical management of 52 ongoing pregnancies: a retrospective review.

OBJECTIVE: Studies have shown that prenatal exome sequencing (PES) improves diagnostic yield in cases of fetal structural malformation. We have retrospectively analysed PES cases from two of the largest fetal medicine centres in the UK to determine the impact of results on management of a pregnancy. DESIGN: A retrospective review of clinical case notes. SETTING: Two tertiary fetal medicine centres. POPULATION: Pregnancies with fetal structural abnormalities referred to clinical genetics via a multidisciplinary team. METHODS: We retrospectively reviewed the notes of all patients who had undergone PES. DNA samples were obtained via chorionic villus sampling or amniocentesis. Variants were filtered using patient-specific panels and interpreted using American College of Medical Genetics guidelines. RESULTS: A molecular diagnosis was made in 42% (18/43) ongoing pregnancies; of this group, there was a significant management implication in 44% (8/18). A positive result contributed to the decision to terminate a pregnancy in 16% (7/43) of cases. A negative result had a significant impact on management in two cases by affirming the decision to continue pregnancy. CONCLUSIONS: We demonstrate that the results of PES can inform pregnancy management. Challenges include variant interpretation with limited phenotype information. These results emphasise the importance of the MDT and collecting phenotype and variant data. As this testing is soon to be widely available, we should look to move beyond diagnostic yield as a measure of the value of PES. TWEETABLE ABSTRACT: Prenatal exome sequencing can aid decision-making in pregnancy management; review ahead of routine implementation in NHS.

A rare and severe case of pronator teres syndrome.

We present the case of a patient with severe symptoms of proximal forearm median nerve neuropathy. Over the course of 5 years his condition progressed to encompass rare features of combined pronator teres syndrome (PTS) and anterior interosseous nerve syndrome (AINS). The aetiology was found to be pronator teres compression and was managed successfully by surgical decompression. Proximal forearm median nerve compression should be considered as a continuum with two classic endpoints. At one end of the spectrum pure PTS presents with solely or mainly sensory symptoms, whereas at the other end AINS presents with pure motor symptoms. Hence, all possible anatomical sites of compression must be surgically explored in all cases of PTS or AINS, regardless of symptomatology. Timely referral to an experienced specialist is encouraged to ensure good outcomes, whenever a primary care practitioner encounters an atypical carpal tunnel syndrome-like presentation.

Transforming the Concept of Memory Reactivation.

Reactivation refers to the phenomenon wherein patterns of neural activity expressed during perceptual experience are re-expressed at a later time, a putative neural marker of memory. Reactivation of perceptual content has been observed across many cortical areas and correlates with objective and subjective expressions of memory in humans. However, because reactivation emphasizes similarities between perceptual and memory-based representations, it obscures differences in how perceptual events and memories are represented. Here, we highlight recent evidence of systematic differences in how (and where) perceptual events and memories are represented in the brain. We argue that neural representations of memories are best thought of as spatially transformed versions of perceptual representations. We consider why spatial transformations occur and identify critical questions for future research.