Exploring the heterogeneous transcriptional response of the CNS to systemic LPS and Poly(I:C).

Peripheral contact to pathogen-associated molecular patterns (PAMPs) evokes a systemic innate immune response which is rapidly relayed to the central nervous system (CNS). The remarkable cellular heterogeneity of the CNS poses a significant challenge to the study of cell type and stimulus dependent responses of neural cells during acute inflammation. Here we utilized single nuclei RNA sequencing (snRNAseq), serum proteome profiling and primary cell culture methods to systematically compare the acute response of the mammalian brain to the bacterial PAMP lipopolysaccharide (LPS) and the viral PAMP polyinosinic:polycytidylic acid (Poly(I:C)), at single cell resolution. Our study unveiled convergent transcriptional cytokine and cellular stress responses in brain vascular and ependymal cells and a downregulation of several key mediators of directed blood brain barrier (BBB) transport. In contrast the neuronal response to PAMPs was limited in acute neuroinflammation. Moreover, our study highlighted the dominant role of IFN signalling upon Poly(I:C) challenge, particularly in cells of the oligodendrocyte lineage. Collectively our study unveils heterogeneous, shared and distinct cell type and stimulus dependent acute responses of the CNS to bacterial and viral PAMP challenges. Our findings highlight inflammation induced dysregulations of BBB-transporter gene expression, suggesting potential translational implications on drug pharmacokinetics variability during acute neuroinflammation. The pronounced dependency of oligodendrocytes on IFN stimulation during viral PAMP challenges, emphasizes their limited molecular viral response repertoire.

Understanding the Co-occurrence of Gambling Disorder and Problematic Pornography Use: Exploring Sociodemographic and Clinical Factors.

The co-occurrence between gambling disorder (GD) and problematic pornography use (PPU) has not yet been explored. Therefore, the present study compared (a) sociodemographic variables, (b) GD-related factors, (c) substance use, (d) psychopathology, (e) personality features, (f) impulsivity, and (g) emotion regulation between individuals with GD (GD group) and those with co-occurring GD and PPU (GD+PPU group). The sample consisted of 359 treatment-seeking individuals with GD: n = 332 individuals had GD only (GD group) and n = 37 individuals had GD and co-occurring PPU (GD+PPU group). GD severity, impulsivity, psychopathology, personality, emotion regulation, and other sociodemographic and clinical variables were assessed. No between-group differences in sociodemographic measures were observed. The GD+PPU group demonstrated greater GD severity and a higher likelihood of substance use compared to those without PPU. Furthermore, the presence of PPU was associated with worse psychopathology, higher impulsivity (except for lack of premeditation and positive urgency), more difficulties in emotion regulation (except for non-acceptance of emotions and limited access to emotions), and a personality profile characterized by lower levels of self-directedness and cooperativeness. The co-occurrence of GD and PPU seems associated with a more dysfunctional clinical profile.

The usefulness of an intervention with a serious video game as a complementary approach to cognitive behavioural therapy in eating disorders: A pilot randomized clinical trial for impulsivity management.

OBJECTIVE: The aim of the present study was to test the usefulness of an add-on serious video game approach (i.e., Playmancer) to treatment as usual (TAU) on reducing impulsive behaviours and psychopathology in individuals diagnosed with an eating disorder (ED). METHOD: Thirty-seven patients diagnosed with an ED according to the DSM-5 were included in the present randomized clinical trial (RCT; study record 35,405 in ClinicalTrials.gov) and were randomly assigned to either the TAU or TAU + Playmancer group. All participants completed a clinical interview. Impulsivity (UPPS-P self reported questionnaire and Stroop task) and general psychopathology (SCL-90-R) measures were assessed at: baseline, 4 weeks into treatment, at the end of TAU (after 16 weeks), and follow-up (2 years). In addition, patients in the experimental group underwent a total of nine sessions with Playmancer over the span of 3 weeks. RESULTS: Patients in both treatment groups (TAU + Playmancer or TAU) improved on Stroop task performance and psychological distress. Additionally, patients in TAU-Playmancer improved on the impulsive trait domain of lack of perseverance. No statistical differences were found regarding treatment outcomes (i.e., treatment adherence and remission of eating symptomatology) when comparing the two treatment groups. CONCLUSION: Our results suggest that the impulsivity associated with EDs should be addressed and could be modified, as some facets of trait impulsivity improved after Playmancer add-on treatment. Yet, there were no significant differences in treatment outcomes when comparing the two groups and further research needs to be conducted.

Psychiatric comorbidities and dehydration are more common in children admitted to the emergency department for eating disorders in the COVID-19 era.

PURPOSE: Since the beginning of COVID-19 pandemic, social distancing and home confinement had a significant impact on children, especially on those with eating disorders (ED). The primary objective of this retrospective study was to describe and analyze the demographic and clinical profiles of children presenting with ED during the COVID-19 pandemic. METHODS: We conducted a retrospective review of clinical charts of patients with ED younger than 18 years who accessed the emergency department of the Bambino Gesù Children's Hospital, Rome, between March 2019 and March 2021. Of these, we reported and compared the demographic, clinical and laboratory data before and after the COVID-19 pandemic and looked for predictors of ED severity. RESULTS: A total of 211 admissions for ED were recorded. The patients, mostly females (86.3%) were on average 14.1 years old. The mean weight loss on admission was 11 kg. Bradycardia was observed in 31.3% of the study sample. 16.6% of patients had an associated psychiatric disorder and 60.2% required psychotropic drugs. 68.7% of the patients required hospitalization. Respectively, 96 and 115 patients were admitted before and during the COVID-19 pandemic. The latter were hospitalized more (78.3 vs 57.3%; p = 0.001), yet for less time (19 vs 26 days; p = 0.004), had a higher mean serum creatinine (0.68 vs 0.47; p < 0.001) and were more frequently diagnosed with an associated psychiatric disorder (23.5 vs 8.3%; p = 0.003). CONCLUSION: Our study shows a significant increase of hospitalizations of children with ED during the COVID-19 pandemic, along with a shorter length of stay, more psychiatric comorbidities, and some distinctive features at the laboratory work-up, such as an increase of serum creatinine and/or a reduction of serum albumin. LEVEL OF EVIDENCE: III, evidence obtained from well-designed cohort or case-control analytic studies.

The Severity of Gambling and Gambling Related Cognitions as Predictors of Emotional Regulation and Coping Strategies in Adolescents.

People with gambling disorder (GD) exhibit distorted cognitions and superstitious beliefs more often than the general population. Similarly, difficulties in coping and emotion dysregulation are more prevalent among those with GD, and could determine the onset of GD in particularly vulnerable groups such as adolescents. This study examines the relationship between gambling severity and gambling-related cognitions with coping strategies and emotion regulation. Also, it explores how accurately gambling severity and gambling-related cognitions were able to predict emotion regulation and coping strategies. Two groups were recruited and analyzed: a community sample comprising 250 adolescents and young adults from secondary education schools, and a clinical sample of 31 patients with similar age characteristics seeking treatment for GD. The participants from the clinical sample scored higher on gambling severity, emotion dysregulation, cognitive biases, and maladaptive coping strategies. In the community sample, cognitive biases mediated the relationship between sex and emotion dysregulation and disengagement. People with GD use more often than controls maladaptive emotion regulation strategies to manage negative emotional states. This perspective emphasizes the need to focus on coping with emotions, as opposed to coping with problems, as the best approach to tackle gambling problems.

Exploring the Predictive Value of Gambling Motives, Cognitive Distortions, and Materialism on Problem Gambling Severity in Adolescents and Young Adults.

Gambling motives and cognitive distortions are thought to be associated because both coping and financial motives to gamble appear to be predictors of gambling related cognitive distortions. Therefore, there is an argument to be made that gambling motives, cognitive distortions, and materialism share common attributes and might be related to problem gambling severity. The present paper aims to examine the relationship between these three variables, both in a clinical and community setting, to see if they can predict gambling severity. A sample of 250 participants from the general population and 31 participants from the clinical population was recruited. The results showed that the clinical sample scored higher on gambling severity, cognitive distortions, materialism, and gambling motives. It also showed that low scores in enhancement motives and higher scores in social motives and gambling related cognitions predicted gambling severity in older gamblers, whereas for younger patients, gambling severity was best predicted by higher scores in materialism and coping motives, and lower scores for enhancement and social motives. In the community sample, gambling severity correlated with gambling related cognitive distortions and with gambling motives (except for social and coping motives within the women subsample). These results testify to the importance of materialism, cognitive distortions, and gambling motives as risk factors for problem gambling both in community and clinical samples.

Executive functions in binge spectrum eating disorders with comorbid compulsive buying.

OBJECTIVE: The aims were to explore if bulimic spectrum disorders (BSD) patients, who also present comorbid compulsive buying (CB), could represent a specific subtype considering its neuropsychological performance; to present a descriptive analysis of different clinical features; and to explore how these variables could influence treatment outcome. It was hypothesised that the comorbid group will present worse neuropsychological performance that will lead to a worse treatment outcome. METHOD: The study has a longitudinal design. Women (N = 75) diagnosed with BSD, BSD + CB and Healthy Controls (HC); completed an evaluation of: cognitive flexibility, decision making, eating disorder (ED) symptomatology, psychopathological state and personality traits. RESULTS: BSD + CB was the group with the most severe clinical profile, worst treatment outcome and higher neuropsychological impairment, than other groups. Path-analysis evidenced that deficits in decision making were associated with bad treatment outcome, while deficits in flexibility with the presence of the comorbidity. Self-directedness and novelty seeking were associated with the neuropsychological performance and the comorbidity. CONCLUSION: BSD + CB exhibit a worse clinical and neuropsychological profile that seems to be related with the treatment outcome, which should be taken into account for the establishment of specific treatment approaches.

COVID-19 and eating disorders during confinement: Analysis of factors associated with resilience and aggravation of symptoms.

OBJECTIVES: To assess the level of deterioration in functioning of ED patients during confinement, due to COVID-19, and examine potential contributing factors (coping strategies, anxiety-depressive symptomatology and personality traits). METHODS: A total of 74 ED patients in treatment before the COVID-19 outbreak, contributed to this study. Baseline pre-treatment evaluation included the SCL-90R, TCI-R, EDI-2 and Y-FAS 2.0 questionnaires for general psychopathology, personality and ED severity indexes. ED symptoms, coping strategies, socio-demographic data and COVID-19 concerns were collected by clinicians through a semi-structured telephone survey during lockdown. RESULTS: A deterioration in ED symptoms and general psychopathology (anxiety and depression), during lockdown, was associated with low self-directedness. Higher ED symptomatology during confinement was associated with less-adaptive coping strategies to deal with lockdown situation leading to an increase in weight. CONCLUSIONS: These specific vulnerability factors to further confinement or stressful situations may help design personalized preventive and therapeutic approaches.

Emotional and non-emotional facets of impulsivity in eating disorders: From anorexia nervosa to bulimic spectrum disorders.

OBJECTIVE: Impulsivity and difficulties in regulating emotions are considered to be transdiagnostic characteristics of patients with eating disorders (EDs). The study aimed to investigate trait impulsivity and inhibitory components of impulsivity, related or unrelated to emotions in patients with EDs. METHOD: A total of 17 patients with anorexia nervosa (AN), 16 patients with bulimic-spectrum EDs (BSD) and 20 healthy control (HC) participants completed an impulsivity scale (UPPS-P) before performing an emotional inhibitory control task during electroencephalography (EEG) acquisition. RESULTS: Higher trait impulsivity in EDs than HC (with higher scores among BSD patients) was observed. However, no differences in behavioural measures or neural indexes [event-related potential (ERP)] of emotional and non-emotional inhibitory control were observed between patients and HC. CONCLUSION: The present results highlighted negative urgency, an impulsive personality trait related to emotions, as a common feature of AN and BSD. Lack of perseverance, a trait which is less related to emotions, specifically characterises patients with BSD. On the other hand, behavioural and ERP data did not show altered inhibitory control in EDs, for either general or emotional-related response inhibition.

Psychological predictors of poor weight loss following LSG: relevance of general psychopathology and impulsivity.

PURPOSE: After bariatric surgery (BS) a significant minority of patients do not reach successful weight loss or tend to regain weight. In recent years, interest for the psychological factors that predict post-surgical weight loss has increased with the objective of developing interventions aimed to ameliorate post-surgical outcomes. In the present study, predictive models of successful or poor weight loss 12 months after BS were investigated considering pre-surgery level of psychopathological symptoms, dysfunctional eating behaviors and trait impulsivity at baseline (pre-surgery). METHODS: Sixty-nine patients with morbid obesity canditates for laparoscopic sleeve gastrectomy were assessed regarding metabolic and psychological dimensions. Successful post-surgery weight loss was defined as losing at least 50% of excess body weight (%EWL). RESULTS: Logistic models adjusted for patient sex, age and presence of metabolic diseases showed that the baseline presence of intense psychopathological symptoms and low attentional impulsivity predict poor %EWL (< 50%), as assessed 12-month post-surgery. CONCLUSIONS: The present findings suggest that intensity of general psychopathology and impulsivity, among other psychological factors, might affect post-surgery %EWL. Conducting adequate psychological assessment at baseline of patients candidates for BS seems to be crucial to orient specific therapeutic interventions. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Impulsivity toward food reward is related to BMI: Evidence from intertemporal choice in obese and normal-weight individuals.

Obesity is a medical condition frequently associated with psychopathological symptoms and neurocognitive and/or personality traits related to impulsivity. Impulsivity during intertemporal choices seems to be typical of obese individuals. However, so far, the specific relationship between different types of reward and neuropsychological and psychopathological profile are yet to be unravelled. Here, we investigated impulsive choice for primary and secondary reward in obese individuals and normal-weight controls with comparable neuropsychological and psychopathological status. Participants performed three intertemporal choice tasks involving food, money, and discount voucher, respectively. Moreover, they completed a battery of neuropsychological tests and psychometric questionnaires assessing psychopathological state, impulsivity, and personality traits. Obese individuals showed increased preference for immediate food reward compared with controls, whereas no group difference emerged concerning money and discount voucher. Moreover, the higher the body mass index (BMI), the steeper the food discounting. These findings emerged in light of comparable neuropsychological and psychopathological profile between groups. Steeper food discounting in obese individuals appears to be related to BMI but not to psychopathological and neuropsychological profile. We suggest using intertemporal choice in the clinical practice as measure of the effectiveness of different types of intervention (e.g., educational, psychological, pharmacological or surgical) aimed at reducing impulsivity toward food and increasing cognitive control during food intake in obese individuals.

The Functional Neuroimaging of Autobiographical Memory for Happy Events: A Coordinate-Based Meta-Analysis.

Neuroimaging studies using autobiographical recall methods investigated the neural correlates of happy autobiographical memories (AMs). The scope of the present activation likelihood estimation (ALE) meta-analysis was to quantitatively analyze neuroimaging studies of happy AMs conducted with autobiographical recall paradigms. A total of 17 studies (12 fMRI; 5 PET) on healthy individuals were included in this meta-analysis. During recall of happy life events, consistent activation foci were found in the frontal gyrus, the cingulate cortex, the basal ganglia, the parahippocampus/hippocampus, the hypothalamus, and the thalamus. The result of this quantitative coordinate-based ALE meta-analysis provides an objective view of brain responses associated with AM recollection of happy events, thus identifying brain areas consistently activated across studies. This extended brain network included frontal and limbic regions involved in remembering emotionally relevant positive events. The frontal gyrus and the cingulate cortex may be responsible for cognitive appraisal processes during recollection of happy AMs, while the subthalamic nucleus and globus pallidus may be involved in pleasure reactions associated with recollection of happy life events. These findings shed light on the neural network involved in recalling positive AMs in healthy individuals, opening further avenues for future research in clinical populations with mood disorders.

The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis.

Activation of Bruton's tyrosine kinase (BTK) has been shown to play a crucial role in the proinflammatory response of B cells and myeloid cells upon engagement with B cell, Fc, Toll-like receptor, and distinct chemokine receptors. Previous reports suggest BTK actively contributes to the pathogenesis of multiple sclerosis (MS). The BTK inhibitor Evobrutinib has been shown to reduce the numbers of gadolinium-enhancing lesions and relapses in relapsing-remitting MS patients. In vitro, BTK inhibition resulted in reduced phagocytic activity and modulated BTK-dependent inflammatory signaling of microglia and macrophages. Here, we investigated the protein expression of BTK and CD68 as well as iron accumulation in postmortem control (n = 10) and MS (n = 23) brain tissue, focusing on microglia and macrophages. MS cases encompassed active, chronic active, and inactive lesions. BTK+ and iron+ cells positively correlated across all regions of interests and, along with CD68, revealed highest numbers in the center of active and at the rim of chronic active lesions. We then studied the effect of BTK inhibition in the human immortalized microglia-like HMC3 cell line in vitro. In particular, we loaded HMC3 cells with iron-dextran and subsequently administered the BTK inhibitor Evobrutinib. Iron treatment alone induced a proinflammatory phenotype and increased the expression of iron importers as well as the intracellular iron storage protein ferritin light chain (FTL). BTK inhibition of iron-laden cells dampened the expression of microglia-related inflammatory genes as well as iron-importers, whereas the iron-exporter ferroportin was upregulated. Our data suggest that BTK inhibition not only dampens the proinflammatory response but also reduces iron import and storage in activated microglia and macrophages with possible implications on microglial iron accumulation in chronic active lesions in MS.

Craving in gambling disorder: A systematic review.

Background and objectives: Craving is one of the main criteria for the diagnosis of substance use disorder according to the DSM-5; however, it is not included in the main criteria for gambling disorder (GD). In the present systematic review, we aimed to evaluate the available body of knowledge regarding gambling craving to help step forward to a consensus regarding this topic. Data sources: PsycINFO/PsycARTICLES and PubMed/Medline were used. Study eligibility criteria, participants, and interventions: (1) individuals of both genders who had a clinical diagnosis of GD in which the presence of gambling craving were studied by means of tasks or self-report tools; (2) we included three types of studies: (a) validation articles of craving psychometric tools in which GD was assessed; (b) articles in which craving-GD association was explored; and (c) treatment articles for GD in which craving was assessed. Results: n = 63 studies were finally included in the systematic review. Some studies described an association between craving- and gambling-related factors, and craving was also described as a predictor of GD severity, gambling episodes, chasing persistence and income-generating offenses. Gambling craving also seems to be associated with emotional states and negative urgency. Finally, some studies implemented specific interventions for GD and assessed its impact on reducing gambling craving. Conclusions: There is a growing body of knowledge on the relevant role of craving in gambling behavior and GD. Further studies are needed to reach a consensus on the diagnostic criterion for GD.

Periodontitis prevalence and severity in inflammatory bowel disease: A case-control study.

BACKGROUND: Recent evidence is supporting the notion of a microbiological and immunological continuum on the gum-gut axis in health and disease. Therefore, the purpose of this study was to assess the prevalence and risk indicators of periodontitis in patients with Crohn's disease (CD) or ulcerative colitis (UC) compared to age- and sex-matched controls without inflammatory bowel disease (IBD). METHODS: A total of 180 IBD (117 CD, 60 UC, 3 IBD-unclassified) and 180 healthy controls were compared for their periodontitis diagnosis (Centers for Disease Control and Prevention/American Academy of Periodontology [CDC/AAP] case definition) and full-mouth periodontal parameters. In addition, explorative logistic regression models were performed. RESULTS: Significantly more patients with IBD had moderate/severe periodontitis (85.6% vs. 65.6%, p < 0.001) and severe periodontitis (36.7% vs. 25.6%, p < 0.001) than controls. Differences were higher in the 35-50 and 51-65 age groups, without significant changes between CD and UC. IBD subjects presented chances ∼3.5 higher of having moderate/severe periodontitis (p < 0.001). Significant variables associated with periodontitis in the whole sample were older age, presence of IBD, and higher full-mouth plaque scores, whereas in the IBD group they were male sex, IBD-associated surgery, and IBD duration and localization (pancolitis). Positive risk indicators for IBD were periodontitis severity and higher bleeding scores, while smoking was negatively associated with UC. CONCLUSIONS: Relevant associations between IBD and periodontitis were found, being modified by CD and UC clinical characteristics. Preventive and therapeutic strategies involving the gum-gut axis should be enforced in IBD patients.

Early Naso-Gastric Feeding and Outcomes of Anorexia Nervosa Patients.

Nutritional rehabilitation with weight restoration is an important step in patients hospitalised for anorexia nervosa (AN). Naso-gastric feeding (NGF) should be considered when oral nutrition (OF) and oral nutritional supplementation (ONS) are insufficient. We evaluated the role of NGF on short- and long-term outcomes, considering weight gain, the length of hospitalisation (LOS) and the time to relapse. We report on the characteristics of patients under 18 years of age with AN admitted to the Department of Emergency and Acceptance of the Bambino Gesù Children's Hospital, IRCCS, Rome, between March 2019 and August 2022. Three hundred and fifteen patients were enrolled. We compared patients treated with NGF (group A) and patients without NGF (group B). Group A was characterised by a significantly lower BMI on admission and discharge, more frequent use of inpatient psychotropic therapy (IPDT) and longer hospital stay. The time to relapse was significantly longer in group A compared to group B. An early NGF setting correlates with a longer time to relapse and may be associated with a shorter LOS. A high caloric intake with a balanced nutritional formula provided by NGF allows an earlier recovery. The main advantages of this approach could be the rapid discharge of patients and a more effective psychological and social recovery.

Treatment of antibiotic refractory chronic pouchitis with JAK inhibitors and S1P receptor modulators: an ECCO CONFER Multicentre Case Series.

BACKGROUND AND AIMS: Data regarding effectiveness and safety of JAK inhibitors and S1P receptor modulators in antibiotic refractory chronic pouchitis (CARP) are lacking. METHODS: This ECCO-CONFER project retrospectively collected JAK inhibitors or S1P receptor modulators treatments for CARP with at least 3-months follow up. The outcomes included corticosteroid and antibiotics-free clinical response and remission at three and twelve months, trend in mPDAI, endoscopic PDAI, CRP and calprotectin. RESULTS: Seventeen treatments in 15 patients were collected. Previous pouchitis treatments included infliximab (5/15), adalimumab (4/15), vedolizumab (9/15), and ustekinumab (5/15). Pooling data on JAK inhibitors (8 tofacitinib, 1 filgotinib and 6 upadacitinib), after 3 months (T3), steroid and antibiotics-free clinical response was achieved in 53.3% (8/15), steroid and antibiotics-free clinical remission was achieved in 40% (6/15). Of the patients with at least 12 months of follow-up, steroid and antibiotics-free clinical response was achieved in 50% (3/6) and remission in one patient (16.7%), endoscopic response in 50% (3/6), endoscopic remission in 50% (3/6). Of the two ozanimod treatments at T3, steroid and antibiotics-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects reported. CONCLUSIONS: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation.

Patients with inflammatory bowel disease are at increased risk of atherothrombotic disease: A systematic review with meta-analysis.

AIMS: Patients with inflammatory bowel disease (IBD) are known to be at increased risk for venous thrombosis, while their risk for arterial ischemic events is debated. The purpose of this study was to conduct a systematic review of the published literature on the risk of myocardial infarction (MI) in IBD patients and to identify any potential risk factors. METHODS: The present study was performed according to PRISMA, with a systematic search on PubMed, Cochrane, and Google Scholar. Risk of MI was the primary end point, while all causes of death and stroke were secondary endpoints. Both univariate and multivariate pooled analysis were performed. RESULTS: An overall population of 515,455 controls and 77,140 persons with IBD (26,852, 34.8% Crohn's disease, CD and 50,288, 65.2% ulcerative colitis, UC) was included. Mean age was similar across controls and IBD. Persons with CD and UC had lower rates of hypertension (14.5% vs. 14.6% vs. 25%), diabetes (2.9% vs. 5.2% vs. 9.2%) and dyslipidaemia (3.3% vs. 6.5% vs. 16.1%) compared to controls. Smoking did not significantly differ (17% vs. 17.5% vs. 10.6%). Pooled results of multivariate adjustment showed that, after a 5 years-follow-up, both CD and UC were at increased risk of MI (respectively HR 1.36 [1.12-1.64] and HR 1.24 [1.05-1.46]), of death (HR 1.55 [1.27-1.90] and HR 1.29 [1.01-1.64]), and of other CV disease as stroke (HR 1.22 [1.01-1.49] and HR 1.09 [1.03-1.15], all 95% CI). CONCLUSIONS: Persons with IBD are at increased risk of MI, despite a lower prevalence of the classic risk factors for MI (hypertension, diabetes, dyslipidemia).

Single nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke.

Reactive neuroglia critically shape the brains response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition and microenvironment of the early ischemic lesion. Here we generated a single cell resolution transcriptomics dataset of the injured brain during the acute recovery from permanent middle cerebral artery occlusion. This approach unveiled infarction and subtype specific molecular signatures in oligodendrocyte lineage cells and astrocytes, which ranged among the most transcriptionally perturbed cell types in our dataset. Specifically, we characterized and compared infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and heterogeneous reactive astrocyte populations. Our analyses unveiled unexpected commonalities in the transcriptional response of oligodendrocyte lineage cells and astrocytes to ischemic injury. Moreover, OPCs and reactive astrocytes were involved in a shared immuno-glial cross talk with stroke specific myeloid cells. In situ, osteopontin positive myeloid cells accumulated in close proximity to proliferating OPCs and reactive astrocytes, which expressed the osteopontin receptor CD44, within the perilesional zone specifically. In vitro, osteopontin increased the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition and microenvironment of infarcted brain tissue in the early stages of recovery.

Maintainance of diagnostic Laboratory during pandemic emergency (SARS-CoV-2) in a Small Hospital.

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