Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval+extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval+extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization). Our results demonstrate that extinction and retrieval+extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rats

Psoriasis and Psoriatic Arthritis in the Context of the COVID-19 Pandemic: A Plenary Session From the GRAPPA 2020 Annual Meeting.

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall

Consensus terminology for preclinical phases of psoriatic arthritis for use in research studies: results from a Delphi consensus study.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: \u27increased risk for PsA\u27, \u27psoriasis with asymptomatic synovio-entheseal imaging abnormalities\u27 and \u27psoriasis with musculoskeletal symptoms not explained by other diagnosis\u27. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated

Efficacy of guselkumab, a selective IL-23 inhibitor, in Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA): protocol of a randomised, double-blind, placebo controlled multicentre trial

Introduction Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5–7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA)-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression.Methods and analysis The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints.Ethics and dissemination Ethics approval for this study was granted by the coordinating centre’s (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations.Trial registration number NCT05004727

Clinical validation of digital assessment tools and machine learning models for remote measurement of psoriasis and psoriatic arthritis: a proof-of-concept study

Objective Psoricatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, smartphone sensor-based assessments that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. Methods Participants with psoriasis, psoriatic arthritis, or healthy controls were recruited between June 5, 2019, and November 10, 2021, at two academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. Results Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD: 12.6). Seventy-nine (76%) participants had psoriatic arthritis, 16 (15.4%) had psoriasis and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with psoriasis demonstrated very strong concordance (CCC = 0.94, [95%CI = 0.91–0.96]) with physician-assessed BSA. The in-clinic and remote target-lesion Physician Global Assessments showed fair to moderate concordance (CCC erythema =0.72 [0.59–0.85]; CCC induration =0.72 [0.62–0.82]; CCC scaling =0.60 [0.48–0.72]). Machine learning models of hand photos taken by patients accurately identified clinically-diagnosed nail psoriasis with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC = 0.68 (0.47–0.85)). Conclusion The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.info:eu-repo/semantics/publishe

Treatment Strategies Targeting Excess Hippocampal Activity Benefit Aged Rats with Cognitive Impairment

Excess neural activity in the CA3 region of the hippocampus has been linked to memory impairment in aged rats. We tested whether interventions aimed at reducing this excess activity would improve memory performance. Aged (24 to 28 months old) male Long–Evans rats were characterized in a spatial memory task known to depend on the functional integrity of the hippocampus, such that aged rats with identified memory impairment were used in a series of experiments. Overexpression of the inhibitory neuropeptide Y 13–36 in the CA3 via adeno-associated viral transduction was found to improve hippocampal-dependent long-term memory in aged rats, which had been characterized with impairment. Subsequent experiments with two commonly used antiepileptic agents, sodium valproate and levetiracetam, similarly produced dose-dependent memory improvement in such aged rats. Improved spatial memory with low doses of these agents was observed in both appetitve and aversive spatial tasks. The benefits of these different modalities of treatment are consistent with the concept that excess activity in the CA3 region of the hippocampus is a dysfunctional condition that may have a key role underlying age-related impairment in hippocampal-dependent memory processes. Because increased hippocampal activation occurs in age-related memory impairment in humans as observed in functional neuroimaging, the current findings also suggest that low doses of certain antiepileptic drugs in cognitively impaired elderly humans may have therapeutic potential and point to novel targets for this indication

Ecology under lake ice

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experi-ence periods of snow and ice cover. Relatively little is known of winter ecology in these systems,due to a historical research focus on summer ‘growing seasons’. We executed the first global quan-titative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42research groups and 101 lakes, examining seasonal differences and connections as well as how sea-sonal differences vary with geophysical factors. Plankton were more abundant under ice thanexpected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summerphytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concen-trations were typically higher during winter, and these differences were exaggerated in smallerlakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), withhigher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplanktonand zooplankton community composition showed few systematic differences between seasons,although literature suggests that seasonal differences are frequently lake-specific, species-specific,or occur at the level of functional group. Within the subset of lakes that had longer time series,winter influenced the subsequent summer for some nutrient variables and zooplankton biomas