Clinical and Humanistic Burden of IgAN in Adult Patients: A Global Real-World Survey.

Background: Immunoglobulin A nephropathy (IgAN) is a chronic, progressive kidney disease in which proteinuria, reduced estimated glomerular filtration rate (eGFR), pain and fatigue are common. How symptoms interact and impact patient quality of life (QoL) in real-world practice is poorly studied. This study investigated how patient and physician symptom perceptions differ and how proteinuria and eGFR correlate with pain, fatigue, and QoL in adult IgAN patients.

Measuring human context fear conditioning and retention after consolidation.

Fear conditioning is a laboratory paradigm commonly used to investigate aversive learning and memory. In context fear conditioning, a configuration of elemental cues (conditioned stimulus [CTX]) predicts an aversive event (unconditioned stimulus [US]). To quantify context fear acquisition in humans, previous work has used startle eyeblink responses (SEBRs), skin conductance responses (SCRs), and verbal reports, but different quantification methods have rarely been compared.

Long Lasting Antibodies From Convalescent Pertussis Patients Induce ROS Production and Bacterial Killing by Human Neutrophils.

Pertussis is a respiratory infection caused by the Gram-negative bacterium . Despite high vaccination coverage this disease remains a public health concern worldwide. A better understanding of the protective immune responses to is required for the development of improved vaccines.

Stick or twist? Cost-effectiveness of siponimod compared with continuing existing disease-modifying therapies in the treatment of active secondary progressive multiple sclerosis in the UK.

Objective: Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated.

Negative cognitive schema modification as mediator of symptom improvement after electroconvulsive therapy in major depressive disorder.

Background: Electroconvulsive therapy (ECT) is a potent option for treatment-resistant major depressive disorder (MDD). Cognitive models of depression posit that negative cognitions and underlying all-or-nothing negative schemas contribute to and perpetuate depressed mood. This study investigates whether ECT can modify negative schemas, potentially via memory reactivation, and whether such changes are related to MDD symptom improvement.

Bordetella pertussis-infected innate immune cells drive the anti-pertussis response of human airway epithelium.

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis. This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to B.

Transition to secondary progressive multiple sclerosis: The consequences for patients and healthcare systems, a healthcare professional survey.

Background And Aims: Transition to secondary progressive multiple sclerosis (SPMS) from relapsing-remitting MS (RRMS) is an expected part of the disease trajectory for most patients. However, the transition is challenging to identify due to the gradual nature of progression, and the complications of superimposed relapses, comorbidities, and natural variability in symptoms. This healthcare professional (HCP) survey sought to characterize the transition to and management of SPMS in UK clinical practice.

Naturally circulating pertactin-deficient strains induce distinct gene expression and inflammatory signatures in human dendritic cells.

Respiratory infections caused by are reemerging despite high pertussis vaccination coverage. Since the introduction of the acellular pertussis vaccine in the late twentieth century, circulating strains increasingly lack expression of the vaccine component pertactin (Prn). In some countries, up to 90% of the circulating strains are deficient in Prn.

A reminder before extinction failed to prevent the return of conditioned threat responses irrespective of threat memory intensity in rats.

After retrieval, reactivated memories may destabilize and require restabilization processes to persist, referred to as reconsolidation. The reminder-extinction procedure has been proposed as a behavioral reconsolidation-based intervention to persistently attenuate threat-conditioned memories. After the presentation of a single reminder trial, the conditioned threat memory may enter a labile state, and extinction training during this window can prevent the return of conditioned threat responses.

Investigating the efficacy of the reminder-extinction procedure to disrupt contextual threat memories in humans using immersive Virtual Reality.

Upon reactivation, consolidated memories can enter a temporary labile state and require restabilisation, known as reconsolidation. Interventions during this reconsolidation period can disrupt the reactivated memory. However, it is unclear whether different kinds of memory that depend on distinct brain regions all undergo reconsolidation.

Computed Tomography Thermography for Ablation Zone Prediction in Microwave Ablation and Cryoablation: Advantages and Challenges in an Ex Vivo Porcine Liver Model.

Purpose: The aim of this study was to investigate the diagnostic accuracy of computed tomography (CT) for the prediction of ablation zones from microwave ablation (MWA) and cryoablation (CA) in an ex vivo porcine liver model.

Methods: Sequential (30 seconds) CT scans were acquired during and after MWA and CA in an ex vivo porcine liver model. We generated 120-kVp equivalent reconstructions of generic dual-energy CT data sets, and comprehensive region-of-interest measurements were statistically correlated with invasive temperature monitoring using Pearson correlation coefficient.

Effectiveness of Emotional Memory Reactivation vs Control Memory Reactivation Before Electroconvulsive Therapy in Adult Patients With Depressive Disorder: A Randomized Clinical Trial.

Importance: Although electroconvulsive therapy (ECT) is often effective, approximately half of patients with depression undergoing ECT do not benefit sufficiently, and relapse rates are high. ECT sessions have been shown to weaken reactivated memories. The effect of emotional memory retrieval on cognitive schemas remains unknown.

Activation of Human NK Cells by Requires Inflammasome Activation in Macrophages.

Pertussis is a highly contagious respiratory infection caused by the bacterium . Humans are the only known natural reservoir of . In mice, macrophages and NK cells have a key role in confining to the respiratory tract.

Action boosts episodic memory encoding in humans via engagement of a noradrenergic system.

We are constantly interacting with our environment whilst we encode memories. However, how actions influence memory formation remains poorly understood. Goal-directed movement engages the locus coeruleus (LC), the main source of noradrenaline in the brain.

Episodic memory and Pavlovian conditioning: ships passing in the night.

Research on emotional learning and memory is traditionally approached from one of two directions: episodic memory and classical conditioning. These approaches differ substantially in methodology and intellectual tradition. Here, we offer a new approach to the study of emotional memory in humans that involves integrating theoretical knowledge and experimental techniques from these seemingly distinct fields.

Patients with dorsolateral prefrontal cortex lesions are capable of discriminatory threat learning but appear impaired in cognitive regulation of subjective fear.

Humans are able to cognitively regulate emotions by changing their thoughts. Neuroimaging studies show correlations between dorsolateral prefrontal cortex (dlPFC) activity and cognitive regulation of emotions. Here our objective was to investigate whether dlPFC damage is associated with impaired cognitive regulation of emotion.

Emotional enhancement of memory for neutral information: The complex interplay between arousal, attention, and anticipation.

It can be challenging to explain why certain mundane details circumstantial to an emotional event are nonetheless remembered long after the experience. Here, we examined how attention selectively shapes memory for neutral objects that happen to coincide with either an unexpected or anticipated emotional event. Pictures of neutral objects were presented for 2 s and terminated with either a high-intensity shock, a low-intensity shock, or no shock.

Propofol-induced deep sedation reduces emotional episodic memory reconsolidation in humans.

The adjustment of maladaptive thoughts and behaviors associated with emotional memories is central to treating psychiatric disorders. Recent research, predominantly with laboratory animals, indicates that memories can become temporarily sensitive to modification following reactivation, before undergoing reconsolidation. A method to selectively impair reconsolidation of specific emotional or traumatic memories in humans could translate to an effective treatment for conditions such as posttraumatic stress disorder.

Roles of the Amygdala and Basal Forebrain in Defense: a Reply to Luyck Et al. and Implications for Defensive Action.

The commentary by Luyck and colleagues on our paper provides many stimulating viewpoints and interpretations of our original study on dissociable responses in the amygdala and bed nucleus of the stria terminalis in threat processing. Here, we reply to some of the points raised and while agreeing with most of the comments also provide some alternative viewpoints. We end by putting forward a research agenda for how to further investigate the roles of these regions in threat processing, with an emphasis on studying their roles in defensive action.

Role of Human Ventromedial Prefrontal Cortex in Learning and Recall of Enhanced Extinction.

Standard fear extinction relies on the ventromedial prefrontal cortex (vmPFC) to form a new memory given the omission of threat. Using fMRI in humans, we investigated whether replacing threat with novel neutral outcomes (instead of just omitting threat) facilitates extinction by engaging the vmPFC more effectively than standard extinction. Computational modeling of associability (indexing surprise strength and dynamically modulating learning rates) characterized skin conductance responses and vmPFC activity during novelty-facilitated but not standard extinction.

Threat learning promotes generalization of episodic memory.

The ability to generalize from and distinguish between aversive memories and novel experiences is critical to survival. Previous research has revealed mechanisms underlying generalization of threat-conditioned defensive responses, but little is known about generalization of episodic memory for threatening events. Here we tested if aversive learning influences generalization of episodic memory for threatening events in human adults.

Event segmentation protects emotional memories from competing experiences encoded close in time.

Fear memories are characterized by their permanence and a fierce resistance to unlearning by new experiences. We considered whether this durability involves a process of memory segmentation that separates competing experiences. To address this question, we used an emotional learning task designed to measure recognition memory for category exemplars encoded during competing experiences of fear-conditioning and extinction.

When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing-remitting multiple sclerosis.

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS).

Systematic review of the prevalence of psychiatric illness and sleep disturbance as co-morbidities of HIV infection in the UK.

Psychiatric illness and sleeping disorders are important co-morbidities of human immunodeficiency virus (HIV) infection, which impact both the individual and antiretroviral therapy (ART) selection. This systematic review aimed to assess the prevalence of psychiatric illness and sleep disturbance in people living with HIV (PLHIV) in the UK. Systematic searches for publications reporting epidemiological data for psychiatric co-morbidities and sleep disturbance with HIV were conducted in Embase, MEDLINE, Cochrane Library, eight key conferences (2013-2015), and by hand-searching references of included publications.

How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses.

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce.