Reactivity Scores Research Articles

Toxicity assessment following conventional radiation therapy and pulsed low dose rate radiation therapy: an in vivo animal study

BackgroundPulsed low dose rate radiotherapy (PLDR) is a new radiation delivery method, in which the fractional dose is divided into sub-fractional doses with periodical time breaks in between. The goal of our study is to assess the toxicity on healthy tissues resulting from PLDR as compared to conventional radiotherapy (CRT) using the same physical X-ray dose.MethodsWe analyzed the weight and survival time for CRT and PLDR groups and studied the inflammatory cytokine transforming Growth Factor-β (TGF-β), usually released following irradiation. Histopathological and immunohistochemical analyses were conducted for intestinal and bone marrow tissues from rats subjected to 8 Gy whole- body irradiation using CRT and PLDR techniques. We investigated genotoxicity by performing a comet assay (CA) in splenic tissues.ResultsOur findings showed an improvement in survival time with PLDR versus CRT by 82%.The mean survival time for CRT rats’ group was 6.3 days, while it was 35.9 days for PLDR group.The weight of CRT group decreased gradually by 3.7%, while weight of PLDR group increased gradually by 2.4%.CRT resulted in more cellular atrophy in bone marrow and intestinal tissues than in PLDR treatments as shown by hematoxylin and eosin staining analysis. In addition, the transforming growth factor-β (TGF-β) expression in bone marrow and intestinal tissues of CRT was higher than those expressed in tissues from PLDR as demonstrated by the Immuno reactive score (IRS). It was10(0.53) and 9.8(0.55) for BM and intestinal tissues, respectively from CRT group and 5.8(0.63) for PLDR for both tissues. The measured CA parameters were larger with CRT compared to PLDR, where the Tail Length (TL), Tail DNA % (TD%) and Tail Moment (TM) measurements were 25.4(3.4), 56.5(7.6) % and 20.5(3.5) for CRT, 7.3(1.9), 30.0(7.2) % and 5.7(1.8) for PLDR, with P value 0.000064, 0.0004 and 0.00017, respectively.ConclusionThis study indicates that PLDR can reduce the toxicity on normal tissues compared to CRT.

Move past adversity or bite through it? Diet quality, physical activity, and sedentary behavior in relation to resilience.

Adverse life experiences are associated with an increased risk of mental disorders. The successful adaptation to adversity and maintenance or quick restoration of mental health despite adversity is referred to as resilience. Identifying factors that promote resilience can contribute to the prevention of mental disorders. Lifestyle behaviors, increasingly recognized for their impact on mental health, are discussed as potential resilience factors. Several studies found that healthy eating and physical activity (PA) are positively associated with resilience. However, most of these studies assessed resilience through questionnaires, which is unsatisfactory given that resilience research is moving toward conceptualizing resilience as the outcome of a dynamic process, which can only be assessed prospectively and longitudinally. The present study is the first to assess the relationship between diet quality, PA, sedentary behavior (SB), and resilience, captured prospectively and longitudinally in a sample of 145 individuals (75.17% female; Mage = 28.88, SDage = 7.80; MBMI = 24.11, SDBMI = 3.97). Resilience was assessed as the relationship between stressor exposure and mental health (i.e., the stressor reactivity score: higher scores indicate lower resilience and vice versa). Diet quality (i.e., the Healthy Eating Index) was assessed on the basis of app-based food records and 24-hr dietary recalls. PA and SB were objectively recorded through accelerometers. Regression analysis showed that neither diet quality nor PA and SB predicted resilience (ps > .30). Profound differences in the conceptualization and operationalization of resilience might explain the contrary findings. Prospective longitudinal studies are needed to replicate the findings of the present study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The role of leukocyte activation in suspected Non-IgE excipient-related COVID-19 vaccine reactions: An exploratory hypothesis-driven study of pathogenesis.

Background: Adverse allergic reactions due to the administration of vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns in December 15, 2020. Current analyses provided by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of messenger RNA (mRNA) 1273 and BNT162b2 vaccines administered, respectively. The mechanisms by which these mRNA vaccines induce adverse vaccine reactions have been the subject of conflicting reports. Although skin testing with excipient components found in mRNA-1273 and BNT162b2 vaccines, such as polyethylene glycol (PEG) and related vaccine lipid products, were originally recommended to identify potential predictive biomarkers of adverse allergic reactions, more recent evidence has suggested that routine skin testing with these vaccine excipients have poor predictability and do not correlate with susceptibility to vaccine injury. Objective: The goal of this proof-of-concept (POC) exploratory study was to investigate the role of leukocyte activation (LA) induced by lipid excipients found in mRNA COVID-19 vaccines in the pathogenesis of COVID-19 mRNA vaccine-associated adverse reactions by using an LA assay developed in our laboratory. Results: An LA assay was performed on blood samples obtained from 30 study subjects who were assigned to three study groups: group 1 consisted of 10 subjects who had received an mRNA COVID-19 vaccine and developed a serious vaccine adverse reaction; group 2 consisted of 10 subjects who had received a COVID-19 vaccine and developed a mild adverse reaction; and group 3 consisted of 10 subjects who had not received a COVID-19 vaccine and were asymptomatic. Five excipients were tested in each of the 10 subjects; hence, a potential of 50 reactions could be expressed in each of the three groups. In the subjects in group 1 who had shown clinically severe vaccine effects, 8 of 50 (16%) had severe LA index (LAI) responses (>144.83), 12 of 50 (24%) had moderate LAI responses (87.62 -144.82), and 30 of 50 (60%) had no reaction (0 - 87.61). In the subjects in group 2 who had shown clinically mild vaccine effects, 4 of 50 (8%) had severe LAI responses (>144.83), 9 of 50 (18%) had moderate LAI responses (87.62 -144.82), and 37 of 50 (74%) had no reaction. In the subjects in group 3 who had not received the vaccine and, therefore, had no clinical vaccine effects, 2 of 50 (4%) had severe LAI responses (>144.83), 10 of 50 (20%) had moderate LAI responses (87.62 -144.82), and 38 of 50 (76%) had no reaction LA index (LAI) responses. Conclusion: The results of this exploratory POC study suggest that the measurement of LA induced by PEG and other vaccine-related lipid excipients found in mRNA COVID-19 vaccines may provide a novel and useful predictive biomarker associated with adverse non-immunoglobulin E (IgE) related allergic reactions to these vaccines. The study results also underscore growing concerns related to these non-IgE hypersensitivity reactions and their potential for pathogenesis of adverse vaccine reactions. This is particularly noteworthy because, with the continuing emergence of novel and evolving variants of severe acute respiratory syndrome corona-virus 2 mutants, yearly immunization with mRNA vaccines will most likely be recommended. Although the study was not sufficiently powered to draw definitive conclusions with regard to associations between vaccine-associated COVID-19 reactions and LA, the trends of a more severe set of clinical reactions seen associated with LAI reactivity scores, particularly with ALC-0159 (2-[{polyethylene glycol} 2000]-N,N-ditetradecylacetamide), suggest a potential benefit worthy of exploration in future randomized controlled trials.

Efecto del sexo y variación individual sobre respuestas de comportamiento y desempeño de bovinos Simbrah

The aim of this study was to evaluate the effect of sex and individual variation on the behavioural responses and performance of Simbrah bovines subjected to a habituation process to human interaction and exposure training. Nineteen animals were used (8 females and 11 males). Reactivity was assessed through points in the restraint cage (1-5), a score for cage exit speed (1-2), and body weight in five assessments over 86 days. Linear mixed models and the effect of individual variations were adopted through a linear regression for each animal, using the b coefficients to classify the animals as habituated, neutral and sensitized. The sex of the animal did not affect the reactivity in the restraint cage, or the cage exit speed (p>0.05); however, reactivity decreased from day 16 (p<0.05) in relation to day 0 in both reactivity scores. There were individual differences in reactivity in the restraint cage and in body weight. On this, 74% of the animals became accustomed to the handling procedure, 21% showed neutral responses in the restraint challenge and 5% were sensitized. In turn, all animals gained weight at different levels, with positive, significant b coefficients (p<0.05) and R2 >0.70. In conclusion, the process of habituation to human interaction and exposure training consistently reduced the reactivity of the animals, without altering their productive performance; however, individual differences must be considered during handling procedures.

Stress Resilience And Resilience Factors Across 9 European Samples During The COVID-19 Pandemic

Abstract While many describe changes in mental health over the pandemic, we investigate change in resilience over time during the pandemic. Stress resilience can be operationalised as stressor reactivity, that is, how much a person’s mental health is affected by the stressors that they experience. Utilising the individual participant data (IPD) meta-analyses megadataset available we first define and quantify how many stressors individuals. We then regress this stressor exposure on mental health within each sample to compute each sample’s normative stressor reactivity. Each person’s individual stressor reactivity is then calculated as the residual to this line at each time points. Resilient outcomes can be understood as lower reactivity as this indicates lower susceptibility to stressors. Stressor reactivity (SR) scores control for individual stressor exposure, therefore allowing us to investigate resilience factors during a time in which exposure to macro and micro stressors varied greatly between individuals. Further, SR scores are a harmonised outcome that can easily compared across different samples in the IPD dataset. Using this outcome, we present findings on resilience trajectories and identify factors that are associated with resilient outcomes. We also disentangle the role of current stressor exposure and prior stressors, showing that prior exposure to stressors increases vulnerability in subsequent exposures. Our findings show that stressor reactivity over time was more stable than mental health symptoms during the pandemic, therefore indicating that SR as an outcome offers new insights into the impact of the pandemic.

Histologic Characterization of Tumor-Adjacent Mammary Adipose Tissue in Normal-Weight and Overweight/Obese Patients with Triple-Negative Breast Cancer

Background: Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. Methods: TNBC tissue sections from normal-weight (BMI<25) and overweight/obese patients (BMI≥25) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score. Results: Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI<25: 2.80 vs. BMI≥25: 10.45; p = 0.011) and lower numbers of CD31+ (BMI<25: 4.20 vs. BMI≥25: 2.40; p = 0.018) and CD34+ (BMI<25: 14.60 vs. BMI≥25: 5.20; p = 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI<25: 7.60 vs. BMI≥25: 25.39 in total; p = 0.001). Moreover, expression of CD36 (BMI<25: 2.15 vs. BMI≥25: 2.60; p = 0.041) and ANGPTL4 (BMI<25: 6.00 vs. BMI≥25: 9.80; p = 0.026) was elevated in the TNBC cells of overweight/obese patients. Conclusions: Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment.

GFAP expression in the brain during human postnatal development

AbstractGlial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP‐positive cells (density, GFAP+/mm2), and a reactivity score (R‐score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed‐sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with >60% of infants having an R‐Score >120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region‐dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

Lower extremity muscle activity during reactive balance differs between adults with chronic traumatic brain injury and controls.

Control of reactive balance is key to achieving safe independent walking and engagement in life activities. After traumatic brain injury (TBI), motor impairments and mobility challenges are persistent sequelae. To date, no studies have explored muscle activity of individuals with chronic TBI during a task that requires reactive control of balance. To investigate lower extremity muscle activity during a reactive balance test performed by adults with chronic severe TBI and matched controls. We hypothesized that abnormal activity of lower extremity muscles would be related with poorer reactive balance performance. Also, we performed an exploratory analysis for those with TBI investigating the impact of unilateral versus bilateral lower extremity involvement in the control of reactive balance. Ten adults with chronic severe TBI who were independent community ambulators and ten matched controls performed the computerized reactive balance test (Propriotest®) while lower extremity muscle activity was recorded. Electromyographic (EMG) activity was contrasted (Mann-Whitney U Test) between groups across each 10 s epoch of the 120 s test. Additionally, test scores were correlated (Spearman) with lower extremity composite EMG activity to distinguish muscle activity patterns related with reactive balance performance. Lastly, reactive balance test scores were correlated with reactive balance test scores and clinical functional measures only for the TBI group. Although the TBI group exhibited greater EMG activity across the entire test compared with the control group, significant differences were not observed. Greater composite EMG activity correlated significantly with poorer reactive balance performance across most of the 10 s windows of the test. Greater muscle activity exhibited during the reactive balance test by individuals with chronic severe TBI compared to those without disabilities, particularly at small unexpected perturbations, highlights the greater physiologic effort required to control reactive balance even after independent ambulation is achieved.

Nickel allergy does not correlate with function after total knee arthroplasty.

The purpose of this study is to determine if there is a relationship between clinical outcomes and nickel allergy by evaluating asymptomatic total knee arthroplasty (TKA) patients with well-functioning implants through quantitative metal allergy (MA) testing. A prospective case series was performed on 50 patients with well-functioning TKA of various implant types. Inclusion criteria included primary TKA with a minimum 12-month follow-up and Oxford knee score (OKS) ≥ 40. A commercially available Lymphocyte Transformation Test measured the amount of a hypersensitivity lymphocyte immune response after exposure to a particular antigen. MA results were stratified based on the stimulation index (SI). The Cochran-Mantel-Haenzel test was used to test the homogeneity of metal reactivities. The Wilcoxon-Mann-Whitney test was used to compare individual metal SI by gender and the association of OKS and metal SI was ascertained with the Spearman correlation. Nickel, cobalt, and chromium do not have the same reactivity scores (p < 0.001), and only nickel showed reactive/highly reactive scores. Females were found to have 3.41 times the odds of males for higher Ni reactivity (p = 0.0295, odds ratio [OR], 95% confidence interval [CI] = 3.41 [1.13-10.3]) only. Clinically, there was no correlation between metal SI and OKS score by metal (Ni rho = -0.1779; Co rho = -0.0036; Cr rho = -0.1748). This is the first study looking at MA in well-functioning TKA. There is no correlation between clinical results and nickel reactivity. Surgeons should exercise caution when revising a painful or poorly functioning TKA based solely on a 'positive' Nickel Allergy test and look for other possible reasons for failure. Level II.

A Study on Phubbing, Differentiation of Self and Contribution in Adolescents

The present study examined the phenomenon of "phubbing" in adolescents and its potential impact on the development of self-concept. The study was conducted with 436 individuals using a convenience sampling method. The results of the analyses indicated that there was a significant difference in the contribution to self and community and the total score of participants who were engaged in voluntary activities, and a significant difference in the family, community and total scores of participants who were engaged in activities with their families. The results indicated that there was a significant difference in the total scores of emotional reactivity, self-position, differentiation of self and total scores of self-abstraction, contribution to self, contribution to community and contribution, depending on whether the participants were engaged in an activity that they found enjoyable. Furthermore, it was demonstrated that there was a significant difference in emotional reactivity, family, community and contribution total scores in participants who were engaged in an activity to feel good. This study revealed a partial mediation effect of phubbing between differentiation of self and contribution. The findings of the research were discussed in the context of previous studies and suggestions were made.

The Role of Diet and the Gut Microbiota in Reactive Aggression and Adult ADHD-An Exploratory Analysis.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition, of-ten persistent into adulthood and accompanied by reactive aggression. Associations of diet and the gut-microbiome with ADHD as well as emotional behaviors suggest potential clinical rele-vance of both. However, studies on diet and the gut-microbiome in human reactive aggression are lacking, and should investigate the interaction between diet and the gut-microbiome leading to behavioral changes to assess their potential clinical relevance. In this study, we investigated the interaction of diet and gut-microbiota with adult ADHD and reactive aggression in 77 adults with ADHD and 76 neurotypical individuals. We studied the relationships of ADHD and reactive ag-gression with dietary patterns, bacterial community and taxonomic differences of 16S-sequenced fecal microbiome samples, and potential mediating effects of bacterial genus abundance on signifi-cant diet-behavior associations. The key findings include: (1) An association of high-energy intake with reactive aggeression scores (pFDR = 4.01 × 10-02); (2) Significant associations of several genera with either reactive aggression or ADHD diagnosis with no overlap; and (3) No significant mediation effects of the selected genera on the association of reactive aggression with the high-energy diet. Our results suggest that diet and the microbiome are linked to reactive aggression and/or ADHD individually, and highlight the need to further study the way diet and the gut-microbiome inter-act.

Documenting Compliance and Symptom Reactivity for Ambulatory Assessment Methodology Following Concussion in Adolescents and Young Adults: Feasibility of the Mobile Neurocognitive Health (MNCH) Project.

Evaluate compliance, symptom reactivity, and acceptability/experience ratings for an ecological momentary assessment (EMA) protocol involving ultra-brief ambulatory cognitive assessments in adolescent and young adult patients with concussion. Outpatient concussion clinic. 116 patients aged 13 to 25years with concussion. Prospective research design was used to examine compliance, symptom reactivity, and acceptability/experience for the Mobile Neurocognitive Health Project (MNCH); an EMA study of environmental exposures, symptoms, objective cognitive functioning, and symptom reactivity involving 4, daily EMA surveys (7:30 am, 10:30 am, 3:00 pm, 8:00 pm) for a period of 7 days following concussion. Overall compliance rates, symptom reactivity scores, and participant acceptability/experience ratings were described. A series of non-parametric Friedman Tests with post-hoc Wilcoxon signed-rank tests were used to examine differences in compliance and reactivity related to time of day and over the course of the protocol (first 3 days [Early Week] vs last 4 days [Late Week]). Compliance rates, symptom reactivity scores, participant experience/acceptability. Overall median compliance was 71%, and there were significantly fewer 7:30 am surveys completed compared to the 10:30 am (Z =-4.88,P ≤.001), 3:00 pm (Z =-4.13,P ≤.001), and 8:00 pm (Z =-4.68, P ≤.001) surveys. Compliance for Early Week surveys were significantly higher than Late Week (Z =-2.16,P =.009). The median symptom reactivity score was 34.39 out of 100 and was significantly higher for Early Week compared to Late Week (Z =-4.59,P ≤.001). Ninety-nine percent (89/90) of the sample agreed that the app was easy to use, and 18% (16/90) indicated that the app interfered with their daily life. Adolescents and young adults with concussion were compliant with the MNCH EMA protocol. Symptom reactivity to the protocol was low and the majority of participants reported that the app and protocol were acceptable. These findings support further investigation into applications of EMA for use in concussion studies.

The seeds of change: Antecedent variables and their impact in building grit and resilience through outdoor adventure education.

This study examines the impact of Outdoor Adventure Education (OAE) on developing grit and resilience in adolescents. Focusing on a United States-based sample collected in 2015, it explores how antecedent variables such as age and gender influence these outcomes, integrating the PERMA model of well-being to investigate underlying mechanisms. The research employed a cross-sectional design with 350 participants aged 14-18 from various OAE courses. Data collection involved pre/post surveys assessing grit and resilience as experiences through mastery, relatedness, and emotional reactivity. The study utilized established inventories for grit and the Resilience Scales for Children and Adolescents. Findings revealed significant grit, mastery, and relatedness increases following the OAE program. Participants demonstrated enhanced perseverance and passion toward goals, increased sense of mastery, and better relational dynamics. However, emotional reactivity scores remained largely unchanged. Notably, the impact of these programs varied based on participants' gender and socioeconomic status, indicating differential effects across demographic groups. The study suggests that OAE programs effectively foster grit and resilience in adolescents, with varying impacts based on demographic factors. It highlights the necessity for inclusive and adaptive program designs that cater to diverse participant needs. The results contribute valuable insights to the field of youth development, emphasizing the role of OAE in enhancing key psychological traits essential for adolescents' growth and adaptation.

Quality of human-animal interactions during beef cattle auctions in Panama

This study aimed to determine the quality of human-animal interactions during cattle auctions in Panama and to assess the relationship between cattle reactivity, value paid, and time spent on commercialization. Data were recorded by watching video records of 4531 individual cattle sold in the main Panamanian auctions. Cattle reactivity was assessed by one previously trained observer when the animals entered the box where they were exposed for sale, assigning one of three scores: 1 = calm, 2 = reactive, and 3 = very reactive. Human-animal interactions were assessed using a binary score to assess the occurrence of hitting (1) or not (0) during commercialization. When cattle were hit to stimulate movement, their reactivity was assessed again to determine whether hitting altered their behavior. The value paid (USD/kg of live weight), and the time spent on commercialization (s) of each animal were also recorded in a subsample of 704 animals. Cattle reactivity, genetic group, animal category, auction location and phase of commercialization influenced the occurrence of hits (p<0.05). Hitting altered cattle reactivity (p<0.001); 95 % of the animals scored calm when they entered the auction box, dropped to 85 % after being hit. There was a significant effect of the reactivity score (p<0.05), genetic group (p=0.01), location (p<0.001) and auction phase (p=0.002) on the number of hits received by the cattle when inside the auction box. The median value paid for very reactive cattle tended to be higher than for calm cattle (1.85 vs 1.82 USD/kg; respectively; p=0.06). There were no differences in the time spent on commercialization according to cattle reactivity (p>0.05). In conclusion, cattle reactivity, and auction phase, in addition to other factors such as genetic group, animal category, and auction location, affected the frequency of negative human-animal interactions during commercialization. Cattle reactivity tended to affect the price paid per head of cattle but not the time spent in marketing.

Clinicoradiological Parameters and Biochemical and Molecular Alterations Predicting Remission and Recurrence After Surgical Treatment of Corticotroph Adenomas—Cushing Disease

ObjectivesEndonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas is considered to be the gold standard treatment for Cushing’s Disease (CD). Even with various recent advances in management, disease persistence and recurrences are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64 to 93%. This study aims to determine various clinical, biochemical, radiological and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-kB and SHH pathway activation and to study the protein expression levels of activation markers of these pathways viz. c-Fos , c-Jun, GLI-1 , pMEK, NR4A1 and p44 in functioning corticotroph pituitary adenomas. MethodsFrom January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n=174 surgeries) for Cushing’s disease was ambispectively analysed with a median follow up of 8.1 years (1-13.29 years). The preoperative clinical, biochemical, radiological features, operative findings, postoperative clinical and biochemical data, histopathological and molecular profile, were retrieved from electronic records. The patients were followed up to assess the remission status. ResultsAmong the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for paediatric patients and 12 surgeries were performed in patients with Nelson syndrome. In the primary surgery cohort, 74.3% were females and the average age was 28.73 years (SD 10.15). 75% of the patients experienced remission after primary surgery compared to 47.4% in revision surgery. The remission rate in paediatric patients was 55.5%. Post-operative day 1 plasma cortisol (p<0.001; AUC 0.8894 [0.8087-0.9701]) and ACTH (p<0.001; AUC 0.9 [0.7386-1]) levels were seen to be strong independent predictors of remission in the primary surgery cohort. Remission rates after Endoscopic TSS were more than that after microscopic TSS, in patients undergoing primary surgery (81.08% vs 57.14%; p=0.008). Presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (p=0.020). On categorising based on surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of non-remission (OR 38.1 95% CI 4.2-348.3) compared to endoscopically operated patients with adenoma on HPE. Lower immune reactivity score (IRS) of NR4A1 was found to correlate with higher remission rates (p=0.074). However, none of the molecular markers studied viz. c-Fos , c-Jun, GLI-1, pMEK and p44 showed a significant correlation with the preoperative cortisol values. ConclusionRemission rate after primary surgery is higher as compared to that after revision surgery, and that in paediatric patients is lower as compared to adults. Post-operative day 1 plasma cortisol and ACTH levels are strong independent predictors of remission in the primary surgery cohort. Endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate and thus endoscopy should be the approach of choice in these patients with the goal of identification of an adenoma on histopathological analysis.

Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study.

Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.

Abstract 1087: Cardiovascular Risk Prediction By Platelet Transcriptomics

Background: Hyperreactive platelets are central to atherothrombotic events, including myocardial infarction (MI) and stroke. Currently, no routine clinical test can identify individuals with hyperreactive platelets. The development of a diagnostic platelet hyperreactivity test could identify patients most likely to benefit from antiplatelet therapy to reduce cardiovascular (CV) events. Aim: To develop a diagnostic tool to discriminate platelet hyperreactivity and CV risk. Methods: Platelet aggregation (0.4 μM epinephrine) was assessed by light transmission aggregometry (LTA) and responses &gt;60% were classified as “hyperreactive” and &lt;40% “normoreactive”. Simultaneously, platelet RNA was collected and sequenced (RNA-seq; n=88). Using machine-based learning, a hyperreactive platelet transcriptomic signature was identified, and a Platelet Reactivity ExpreSsion Score (PRESS) was assigned to each participant. Model training performance was evaluated by 10-fold cross-validation. Signature validation was performed in (a) control cohort without CV disease (n=35), and the diagnostic capacity of PRESS was assessed in patients (b) undergoing coronary angiography (n=28) and (c) lower extremity revascularization (LER, n=129). Results: PRESS successfully identified a hyperreactive platelet phenotype in patients with CV disease (AUC 0.81, 95% CI 0.68 - 0.94) and in an independent cohort of healthy participants off antiplatelet therapy (AUC 0.77, 95% CI 0.75 - 0.79). In patients undergoing diagnostic cardiac catheterization, PRESS was significantly higher in patients experiencing an acute MI (β=1.8, adj p=0.02). Among patients undergoing LER, those with a PRESS above the median were more likely to develop a future CV event (adj HR 1.90, CI 1.07 - 3.36, p=0.027). Conclusions: A platelet-derived transcriptomic signature identified individuals with hyperreactive platelets and was associated with increased CV risk. A diagnostic platelet reactivity score may facilitate a personalized approach to antithrombotic therapy for CV risk reduction.

Immunohistochemical and Morphometric Analysis of Lung Tissue in Fatal COVID-19.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

High-risk neighbourhoods and behaviour outcomes in children born extremely preterm.

Study the association between neighbourhood risk and behaviour in extreme preterm (EPT) children. We hypothesised that EPT children living in high-risk neighbourhoods have increased risk of clinical range behaviour problems at age 30-36 months. Retrospective analyses of Child Behavior Checklist (CBCL)scores for 739 EPTs born 2005-2016. Addresses were geocoded to identify census block groups and create high versus low-risk groups. Regression analyses assessed the impact of neighbourhood risk on behaviour. Children from high-risk (N = 272, 39%) and low-risk (N = 417, 61%) neighbourhoods were compared. In adjusted analyses, odds of clinical range scores remained greater in high-risk neighbourhoods for Emotionally Reactive (OR: 4.32, CI: 1.13, 16.51), Somatic Complaints (2.30, CI 1.11,4.79), Withdrawn (OR: 2.56, CI: 1.21, 5,42), Aggressive Behaviour (OR: 4.12, CI: 1.45, 11.68), Internalising (OR: 1.96, CI: 1.17, 3.28), and Total score (OR: 1.86, OR: CI: 1.13, 3.07). Cognitive delay was higher in high-risk neighbourhoods and a risk factor for Attention Problems (2.10,1.08, 4.09). Breast milk was protective for Emotionally Reactive (OR: 0.22, CI: 0.06, 0.85) and Sleep Problems (OR: 0.47, CI:0.24, 0.94). Neighbourhood risk provided an independent contribution to preterm adverse behaviour outcomes with cognitive delay an additional independent risk factor. Breast milk at discharge was protective.

Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.