Macrophages as a Source and Target of GDF-15.

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-ß) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15.

Growth-defense trade-offs promote habitat isolation between recently-diverged species.

Trade-offs are crucial for species divergence and reproductive isolation. Trade-offs between investment in growth versus defense against herbivores are implicated in tropical forest diversity. Empirically exploring the role of growth-defense trade-offs in closely related species' reproductive isolation can clarify the eco-evolutionary dynamics through which growth-defense trade-offs contribute to diversity. Costus villosissimus and C. allenii are recently diverged, interfertile, and partially sympatric neotropical understory plant species primarily isolated by divergent habitat adaptation. This divergent adaptation involves differences in growth rate, which may constrain investment in defense. Here, we investigate growth-defense trade-offs and how they relate to the divergent habitat adaptation that isolates these species. We characterize leaf toughness and chemistry, evaluate the feeding preferences of primary beetle herbivores in controlled trials and field-based experiments, and investigate natural herbivory patterns. We find clear trade-offs between growth and defense: slower-growing C. allenii has tougher leaves and higher defensive chemical concentrations than faster-growing C. villosissimus. Costus villosissimus has rapid growth-based drought avoidance, enabling growth in drier habitats with few specialist herbivores. Therefore, growth-defense trade-offs mediate synergistic biotic and abiotic selection, causing the divergent habitat adaptation that prevents most interspecific mating between C. villosissimus and C. allenii. Our findings advance understanding of ecological speciation by highlighting the interplay of biotic and abiotic selection that dictates the outcome of trade-offs.

Kinin B1 receptor deficiency promotes enhanced adipose tissue thermogenic response to ß3-adrenergic stimulation.

OBJECTIVE AND DESIGN: Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis. MATERIAL OR SUBJECTS: Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure. METHODS: Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice. RESULTS: B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT. CONCLUSION: B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes.

Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.

Assessing the relationship between delay discounting and decisions to engage in various protective behaviors during COVID-19.

Research suggests that discounting of delayed rewards (i.e., tendency to choose smaller immediate rewards over large later rewards) is a promising target of intervention to encourage compliance with public health measures (PHM), such as vaccination compliance. The effects of delay discounting, however, may differ across the types of PHMs, given that the benefits of vaccination, unlike other PHMs (physical distancing, handwashing, and mask-wearing), are more temporally delayed. Here, we examined whether delay discounting predicts engaging in COVID-19 PHMs in approximately 7,000 participants recruited from 13 countries in June-August 2021. After controlling for demographic and distress variables, delay discounting was a negative predictor of vaccination, but a positive predictor of physical distancing (when restrictions are in place) and handwashing. There was no significant association between delay discounting and frequency of mask-wearing. It is possible that increasing vaccination compliance may require greater emphasis on future benefits of vaccination, whereas promotion of physical distancing and hand hygiene may require greater focus on the present moment. Further research is needed to investigate the nature of this relationship and its implications for public health messaging.

"I don't think that a medication is going to help someone long-term stay off opioids": Treatment and recovery beliefs of rural Vermont family members of people with opioid use disorder.

PURPOSE: Few studies have addressed beliefs about treatment for opioid use disorder (OUD) among family members of people with OUD, particularly in rural communities. This study examined the beliefs of rural family members of people with OUD regarding treatment, including medication for OUD (MOUD), and recovery. METHODS: Semi-structured qualitative interviews were conducted with rural Vermont family members of people with OUD. Twenty family members completed interviews, and data were analyzed using thematic analysis. RESULTS: Four primary themes related to beliefs about OUD treatment emerged: (1) MOUD is another form of addiction or dependency and should be used short-term; (2) essential OUD treatment components include residential and mental health services and a strong support network involving family; (3) readiness as a precursor to OUD treatment initiation; and (4) stigma as an impediment to OUD treatment and other health care services. CONCLUSIONS: Rural family members valued mental health services and residential OUD treatment programs while raising concerns about MOUD and stigma in health care and the community. Several themes (e.g., MOUD as another form of addiction, residential treatment, and treatment readiness) were consistent with prior research. The belief that MOUD use should be short-term was inconsistent with the belief that OUD is a disease. Findings suggest a need for improved education on the effectiveness of MOUD for family members and on stigma for health care providers and community members.

Face-off Droop: A Case Report of Pediatric Stroke.

Introduction: Cerebrovascular accidents rarely occur in children; the incidence of ischemic stroke in patients <16 years of age is between 0.6-7.9/100,000. However, they are the fourth most common cause of acute neurological deficits in the pediatric population, and possible cases should be evaluated with a high index of suspicion to ensure timely intervention. Case Report: We describe a previously healthy 17-year-old male who presented to the pediatric emergency department with a left facial droop and hemiparesis consistent with a stroke. The patient's age and lack of comorbidities made this an extremely uncommon presentation. Our patient's neurologic symptoms were believed to have been caused by a recent traumatic clavicular injury sustained two weeks prior, which subsequently led to vascular insult. Conclusion: Cerebrovascular accidents are an important cause of morbidity and mortality in pediatric patients. Cerebrovascular accidents in children are most often secondary to congenital causes; however, care should be taken to assess for acquired causes, such as trauma to major blood vessels. While rarely implicated in traumatic injuries, arterial structures posterior to the medial clavicle can result in severe complications.

Care partners and consumer health information technology: A framework to guide systems-level initiatives in support of digital health equity.

Introduction: Consumer-oriented health information technologies (CHIT) such as the patient portal have a growing role in care delivery redesign initiatives such as the Learning Health System. Care partners commonly navigate CHIT demands alongside persons with complex health and social needs, but their role is not well specified. Methods: We assemble evidence and concepts from the literature describing interpersonal communication, relational coordination theory, and systems-thinking to develop an integrative framework describing the care partner's role in applied CHIT innovations. Our framework describes pathways through which systematic engagement of the care partner affects longitudinal work processes and multi-level outcomes relevant to Learning Health Systems. Results: Our framework is grounded in relational coordination, an emerging theory for understanding the dynamics of coordinating work that emphasizes role-based relationships and communication, and the Systems Engineering Initiative for Patient Safety (SEIPS) model. Cross-cutting work systems geared toward explicit and purposeful support of the care partner role through CHIT may advance work processes by promoting frequent, timely, accurate, problem-solving communication, reinforced by shared goals, shared knowledge, and mutual respect between patients, care partners, and care team. We further contend that systematic engagement of the care partner in longitudinal work processes exerts beneficial effects on care delivery experiences and efficiencies at both individual and organizational levels. We discuss the utility of our framework through the lens of an illustrative case study involving patient portal-mediated pre-visit agenda setting. Conclusions: Our framework can be used to guide applied embedded CHIT interventions that support the care partner role and bring value to Learning Health Systems through advancing digital health equity, improving user experiences, and driving efficiencies through improved coordination within complex work systems.

Optimizing SUV Analysis: A Multicenter Study on Preclinical FDG-PET/CT Highlights the Impact of Standardization.

PURPOSE: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUVmean and SUVmax) of different organs using the same [18F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated. PROCEDURES: In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [18F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol. RESULTS: Without standardization, significant differences in the SUVmean and SUVmax were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability. CONCLUSIONS: The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUVmean and SUVmax values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses.

Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Heatwaves and carbon dioxide enrichment impact invertebrate drift and insect emergence patterns across time in experimental streams.

Climate change and human land use are considered key threats to freshwater invertebrates. Heatwaves can impact the phenology of insects and population dynamics, yet have been largely ignored in experiments compared to mean temperature changes. Another major anthropogenic stressor driving invertebrate community changes is deposited fine sediment; therefore, effects of key climate-change drivers on invertebrate drift and insect emergence rates may differ between sediment-impacted and non-impacted streams. However, this has never been tested in a realistic outdoor experiment. We investigated the individual and combined effects of two 7-day heatwaves, CO2 enrichment, flow velocity variability (periods of fast and slow) and fine sediment on stream drift and emergence responses, sampled four times during a 7-week experiment in 128 flow-through stream mesocosms. We examined invertebrate drift and insect emergence responses to the four stressors, and used these responses to help explain the benthic invertebrate community responses already assessed (sampled at the end of the experiment). Heatwave 1 strongly increased emergence (dominated by Chironomidae), causing an earlier emergence peak, an effect not repeated during heatwave 2, seven days later. During heatwave 1, emerged chironomids were larger in heated channels, but smaller in heated channels afterwards, suggesting a different effect on body size of short-term heatwaves to previous constant warming experiments. CO2 enrichment reduced drifting EPT and total and Chironomidae emergence on three sampling occasions each. After heatwave 1, total drift and total emergence were strongly reduced by heating in ambient-CO2 channels, whereas no reduction occurred in CO2-enriched channels. During heatwave 2, total drift increased in channels without sediment but not in channels with added sediment. Overall, our findings suggest heatwaves can shift the timing of stream insect emergence, regardless of longer-term mean temperatures. They also show that heatwaves, raised CO2, and fine sediment can modulate each others' effects on drift and emergence dynamics.

Electrophysiological Properties and Morphology of Cardiac and Pulmonary Motoneurons within the Dorsal Motor Nucleus of the Vagus of Rats.

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K+ (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.

Sleep-wake behavior, perceived fatigability, and cognitive reserve in older adults.

INTRODUCTION: The effects of sleep-wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR). METHODS: CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis. RESULTS: In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep-related impairments (SRIs), and fatigability at low CR (CRIq < 105.8, p = 0.004) and mean CR (CRIq = 126.9, p = 0.03) but not high CR (CRIq > 145.9, p = 0.65) levels. SRI affected cognitive abilities mediated by fatigability at low CR (p < 0.001) and mean CR (p = 0.003) levels. In healthy controls (n = 13), SRI in fatigability did not alter cognitive abilities across CR levels; controls had higher leisure scores than patients with aMCI (p = 0.003, effect size = 0.93). DISCUSSION: SRI can amplify impaired cognitive abilities through exacerbation of fatigability in patients with aMCI with below-mean CR. Therefore, improving sleep-wake regulation and leisure activities may protect against fatigability and cognitive decline. HIGHLIGHTS: Clinical fatigue and fatigability cannot be alleviated by rest. Clinical fatigability disrupts daily activities during preclinical Alzheimer's. High cognitive reserve mitigates sleep-wake disturbance effects. High cognitive reserve attenuates clinical fatigability effects on daily functioning. Untreated obstructive sleep apnea potentiates Alzheimer's pathology in the brain.

Using Natural Language Processing to Identify Home Health Care Patients at Risk for Diagnosis of Alzheimer's Disease and Related Dementias.

This study aimed to: (1) validate a natural language processing (NLP) system developed for the home health care setting to identify signs and symptoms of Alzheimer's disease and related dementias (ADRD) documented in clinicians' free-text notes; (2) determine whether signs and symptoms detected via NLP help to identify patients at risk of a new ADRD diagnosis within four years after admission. This study applied NLP to a longitudinal dataset including medical record and Medicare claims data for 56,652 home health care patients and Cox proportional hazard models to the subset of 24,874 patients admitted without an ADRD diagnosis. Selected ADRD signs and symptoms were associated with increased risk of a new ADRD diagnosis during follow-up, including: motor issues; hoarding/cluttering; uncooperative behavior; delusions or hallucinations; mention of ADRD disease names; and caregiver stress. NLP can help to identify patients in need of ADRD-related evaluation and support services.

Spirituality/Religion Among First Responders With and Without Posttraumatic Stress Disorder and Alcohol Misuse.

Objective: To examine the co-occurrence of alcohol misuse and posttraumatic stress disorder (PTSD) and potential sources of coping (e.g., spirituality/religion) and clinically relevant variables among first responders (e.g., firefighters, law enforcement corrections officers, paramedics). Method: We assessed rates of independent and co-occurring alcohol misuse and PTSD among a national online sample of 320 first responders as well as the prevalence and salience of S/R, guilt, shame, moral injury, aspects of S/R, and treatment interest. Results: In our sample, 46.88% (n = 150) met criteria for comorbid alcohol misuse and probable PTSD and individuals with these comorbid conditions reported significantly greater negative religious coping, moral injury, and shame than all other diagnostic groups (i.e., independent alcohol misuse, independent PTSD, and neither). Correlations also revealed significant relationships between alcohol misuse and PTSD symptomatology with positive and negative religious coping, moral injury, shame, guilt, interest in treatment, and interest in spiritually integrated treatment. Conclusions: Findings highlight the high rates of independent and co-occurring alcohol misuse and PTSD among first responders as well as the salience of S/R in this population.

Complete genome sequence of Microbacterium paraoxydans phage Damascus.

Phage Damascus was isolated from soil in northwestern Wisconsin using Microbacterium paraoxydans as the host. The Damascus genome is 56,477 bp with 3' single-stranded overhangs and 56.5% G+C content. Damascus was assigned to cluster EL and shares 42.6%-91.7% gene content with the three other phages in this cluster.

Increased sensitivity in detection of deficits following two commonly used animal models of stroke.

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

Multi-tracer PET correlation analysis reveals disease-specific patterns in Parkinson's disease and asymptomatic LRRK2 pathogenic variant carriers compared to healthy controls.

Several genetic pathogenic variants increase the risk of Parkinson's disease (PD) with pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene being among the most common. A joint pattern analysis based on multi-set canonical correlation analysis (MCCA) was utilized to extract PD and LRRK2 pathogenic variant-specific spatial patterns in relation to healthy controls (HCs) from multi-tracer Positron Emission Tomography (PET) data. Spatial patterns were extracted for individual subject cohorts, as well as for pooled subject cohorts, to explore whether complementary spatial patterns of dopaminergic denervation are different in the asymptomatic and symptomatic stages of PD. The MCCA results are also compared to the traditional univariate analysis, which serves as a reference. We identified PD-induced spatial distribution alterations common to DAT and VMAT2 in both asymptomatic LRRK2 pathogenic variant carriers and PD subjects. The inclusion of HCs in the analysis demonstrated that the dominant common PD-induced pattern is related to an overall dopaminergic terminal density denervation, followed by asymmetry and rostro-caudal gradient with deficits in the less affected side still being the best marker of disease progression. The analysis was able to capture a trend towards PD-related patterns in the LRRK2 pathogenic variant carrier cohort with increasing age in line with the known increased risk of this patient cohort to develop PD as they age. The advantage of this method thus resides in its ability to identify not only regional differences in tracer binding between groups, but also common disease-related alterations in the spatial distribution patterns of tracer binding, thus potentially capturing more complex aspects of disease induced alterations.

Reduced Cortical Thickness Correlates of Cognitive Dysfunction in Post-COVID-19 Condition: Insights from a Long-Term Follow-up.

BACKGROUND AND PURPOSE: There is a paucity of data on long-term neuroimaging findings from individuals who have developed the post-coronavirus 2019 (COVID-19) condition. Only 2 studies have investigated the correlations between cognitive assessment results and structural MR imaging in this population. This study aimed to elucidate the long-term cognitive outcomes of participants with the post-COVID-19 condition and to correlate these cognitive findings with structural MR imaging data in the post-COVID-19 condition. MATERIALS AND METHODS: A cohort of 53 participants with the post-COVID-19 condition underwent 3T brain MR imaging with T1 and FLAIR sequences obtained a median of 1.8 years after Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. A comprehensive neuropsychological battery was used to assess several cognitive domains in the same individuals. Correlations between cognitive domains and whole-brain voxel-based morphometry were performed. Different ROIs from FreeSurfer were used to perform the same correlations with other neuroimaging features. RESULTS: According to the Frascati criteria, more than one-half of the participants had deficits in the attentional (55%, n = 29) and executive (59%, n = 31) domains, while 40% (n = 21) had impairment in the memory domain. Only 1 participant (1.89%) showed problems in the visuospatial and visuoconstructive domains. We observed that reduced cortical thickness in the left parahippocampal region (t(48) = 2.28, P = .03) and the right caudal-middle-frontal region (t(48) = 2.20, P = .03) was positively correlated with the memory domain. CONCLUSIONS: Our findings suggest that cognitive impairment in individuals with the post-COVID-19 condition is associated with long-term alterations in the structure of the brain. These macrostructural changes may provide insight into the nature of cognitive symptoms.

Anti-inflammatory, healing and antiophidic potential of Jatropha mollissima (Pohl) Baill. (Euphorbiaceae): From popular use to pharmaceutical formulation in gel.

Jatropha mollissima (Pohl) Baill. (Euphorbiaceae) is widely used in traditional medicine to treat inflammatory disorders. So, a topical gel containing the hydroethanolic extract of its leaves was developed and evaluated for its anti-inflammatory, wound healing, and antiophidic properties in mice. First, the chemical profile of different parts of the plant was characterized by liquid chromatography coupled to mass spectrometry (LC-MS) using molecular networking. In the leaf extract, 11 compounds were characterized, with a particular emphasis on the identification of flavonoids. The gel efficiently inhibited carrageenan-induced paw edema, as well as acute and chronic croton oil-induced ear edema models, thereby reducing inflammatory and oxidative parameters in inflamed tissues. Besides anti-inflammatory activity, the herbal gel showed significant wound healing activity. The edematogenic, hemorrhagic and dermonecrotic activities induced by Bothrops jararaca snake venom were effectively inhibited by the treatment with J. mollissima gel. The association with the herbal gel improved in up to 90% the efficacy of commercial snake antivenom in reduce venom-induced edema. Additionally, while antivenom was not able to inhibit venom-induced dermonecrosis, treatment with herbal gel reduced in 55% the dermonocrotic halo produced. These results demonstrate the pharmacological potential of the herbal gel containing J. mollissima extract, which could be a strong candidate for the development of herbal products that can be used to complement the current antivenom therapy against snake venom local toxicity.