Are There Differences Among Evidence-Based Psychotherapies for Treating Different DSM-5 PTSD Symptom Clusters? A Systematic Review and Meta-analysis of Controlled Clinical Trials.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a heterogeneous disease defined by four Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) symptom clusters: reexperiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. There are effective evidence-based psychotherapies (EBPs) for PTSD. However, given the variety of PTSD clinical presentations, we conducted the first meta-analysis investigating whether DSM-5 PTSD symptom clusters show different responses to EBPs. We systematically reviewed the literature for controlled clinical trials in five databases, performed a meta-analysis, and evaluated the methodological quality of the studies. We screened 633 studies and included seven. Three showed high risk, two showed some concerns, and one showed a low risk of bias. The symptom clusters do not seem to respond differently to EBPs (SMD cluster B: -0.40; 95% confidence interval [CI], -0.87 to 0.08; cluster C: -0.49; 95% CI, -0.90 to -0.08; cluster D: -0.44; 95% CI, -0.94 to 0.05; cluster E: -0.54; 95% CI, -1.07 to -0.0), even when analyzed by the therapeutic focuses. The findings dovetail nicely with the network theory of PTSD symptom, as although it is a heterogeneous disorder, the EBPs seem to promote a kind of cascade of symptom improvement.

An investigation of the predominant structure of antibiotic azithromycin in chloroform solution through NMR and thermodynamic analysis.

Azithromycin (AZM) is a well-known macrolide-type antibiotic that has been used in the treatment of infections and inflammations. Knowledge of the predominant molecular structure in solution is a prerequisite for an understanding of the interactions of the drug in biological media. Experimental structural determination can be carried out for samples in solid-state (X-ray diffraction technique) and gas phase (electron diffraction experiment). In solution, spectroscopic methods can be used to extract valuable information which combined with quantum chemical calculations can lead to the determination of the preferred molecular structures to be observed when a given solute is dissolved in each solvent. That is precisely the aim of this work. We used experimental NMR chemical shift data (in CDCl3) as a reference for comparison with Density Functional Theory (DFT) NMR calculations, with geometry optimized having as guess input two crystallographic structures available in the literature with the configuration of all chiral carbon atoms inverted, named here A and B. The Polarizable Continuum Model (PCM) was used to describe the solvent effects (chloroform) including five explicit CHCl3 solvent molecules, which we believe can account for short and long-range solute-solvent interactions. Analysis of calculated thermodynamic, NMR chemical shift, MAE (Mean Absolute Error), and spin-spin coupling constant values revealed that both supposable C3R-C5S (named M2-A) and C3S-C5R (named M2-B) structures are equally probable to exist in chloroform solution. In addition, we found that the heavy atoms' conformation is reasonably similar in the solid-state and chloroform solution; however, regarding the OH groups, the spatial orientations are rather different with intramolecular OH⋯N and OH⋯O hydrogen bonds present in solution and with some of them being absent in the X-ray structure probably due to crystal packing effects.

The importance of body weight status on motor competence development: From preschool to middle childhood.

We evaluated the association between weight status and motor competence from preschool age (3-5 years of age) until middle childhood (7-9 years of age). Longitudinal study with three to five-year-old preschool children (n = 1155) enrolled in public and private preschools in Recife, Brazil. Children were followed twice (2010, 2012, and 2014) for four years. Köperkoordinationstest für kinder (KTK) assessed the children's motor competence (KTK Motor Quotient). Weight status (underweight, normal weight, overweight, and obesity) was classified according to the children's sex and age. Preschool children with normal weight exhibited higher motor competence at 5-7 years of age compared to preschool children with overweight (+3.73 MQ, P = .03) and obesity (+5.09 MQ, P < .01). Preschool children with normal weight presented higher motor competence at 7-9 years of age compared to their peers with overweight (+6.00 MQ, P = .03) and obesity (+5.88 MQ, P = .01). Children with normal weight at 5-7 years of age presented higher motor competence at 7-9 years of age compared to their peers with overweight (+3.33 MQ, P = .02) and obesity (+4.00 MQ, P = .02). Independent of the childhood phase and extension of the period evaluated (2- or 4-year period), children who had excessive weight (overweight or obesity) and changed their weight status to underweight or normal weight presented similar motor competence compared to children who continued underweight or normal weight. Weight status already at preschool age is an important predictor of the children's motor competence until middle childhood. Interventions improving the children's weight status, already at preschool age, might impact their motor competence development positively.

Absence of definitive scientific evidence that benzodiazepines could hinder the efficacy of exposure-based interventions in adults with anxiety or posttraumatic stress disorders: A systematic review of randomized clinical trials.

BACKGROUND AND OBJECTIVES: Exposure-based interventions (EBIs) are the first-line treatment for anxiety disorders and posttraumatic stress disorder. Although common, the association between EBIs and benzodiazepines is controversial. Therefore, we systematically reviewed the literature to evaluate if benzodiazepines could undermine the efficacy of EBIs in treating these disorders. METHODS: We conducted a systematic review aiming for randomized clinical trials (RCTs) in ISI Web of Science, Scopus, PubMed/MEDLINE, and PsycINFO databases. We scrutinized the reference list of selected papers and other systematic reviews. Finally, we evaluated the methodological quality and the scientific evidence of the studies. RESULTS: We screened 1,529 studies and included 12 RCTs in this review (all showing some concerns or high risk of bias). Benzodiazepines did not impact the efficacy of EBIs in nine studies at posttreatment, improved efficacy in two, and reduced it in one. In the follow-up, benzodiazepines (after its discontinuation) did not impact the efficacy in six studies and reduced it in five. The scientific level of evidence achieved was B for both phases. CONCLUSIONS: Until now there is no definitive evidence that benzodiazepines could hinder the EBIs' efficacy for treating posttraumatic stress disorder and anxiety disorders.

Water Solvent Effect on Theoretical Evaluation of 1H NMR Chemical Shifts: o-Methyl-Inositol Isomer.

In this paper, density functional theory calculations of nuclear magnetic resonance (NMR) chemical shifts for l-quebrachitol isomer, previously studied in our group, are reported with the aim of investigating in more detail the water solvent effect on the prediction of 1H NMR spectra. In order to include explicit water molecules, 20 water-l-quebrachitol configurations obtained from Monte Carlo simulation were selected to perform geometry optimizations using the effective fragment potential method encompassing 60 water molecules around the solute. The solvated solute optimized geometries were then used in B3LYP/6-311+G(2d,p) NMR calculations with PCM-water. The inclusion of explicit solvent in the B3LYP NMR calculations resulted in large changes in the 1H NMR profiles. We found a remarkable improvement in the agreement with experimental NMR profiles when the explicit hydrated l-quebrachitol structure is used in B3LYP 1H NMR calculations, yielding a mean absolute error (MAE) of only 0.07 ppm, much lower than reported previously for the gas phase optimized structure (MAE = 0.11 ppm). In addition, a very improved match between theoretical and experimental 1H NMR spectrum measured in D2O was achieved with the new hydrated optimized l-quebrachitol structure, showing that a fine-tuning of the theoretical NMR spectra can be accomplished once solvent effects are properly considered.

The worldwide incidence of neonaticide: a systematic review.

Neonaticide is the killing of a neonate on the day of its birth by his/her own mother. Neonaticidal women were reported to be predominantly young, unmarried, and primiparous. The motive for murdering the newborn relates to the shame, the fear of rejection, and abandonment by significant others, and the social stigmas associated with an illegitimate birth. The goal of the present study was to conduct a systematic review of the scientific literature and identify population-based studies reporting the incidence of neonaticide in different countries. A total of 485 abstracts were screened. After applying the inclusion/exclusion criteria, 10 studies were selected. Additional searches identified two more articles. Most of these studies were from Europe, where incidence varied from 0.07 (Finland, 1980-2000 period) to 8.5 neonaticides per 100000 births (Austria, 1975-2001 period). More recent studies have indicated that a growing proportion of neonaticidal women are married, multiparous, and suffers from mental disorders. Preventive measures, such as anonymous free delivery, were shown to reduce the incidence of neonaticide, although this effect may be short-lived. Despite social and institutional changes, neonaticide persists even in the most socially advanced, liberal, and prosperous societies in the world.

Lagged influence of North Atlantic Oscillation on population dynamics of a Mediterranean terrestrial salamander.

The North Atlantic Oscillation (NAO) is a large-scale climatic pattern that strongly influences the atmospheric circulation in the northern Hemisphere and by consequence the long-term variability of marine and terrestrial ecosystem over great part of northern Europe and western Mediterranean. In the Mediterranean, the effects of the NAO on vertebrates has been studied mainly on bird populations but was rarely analysed in ectothermic animals, and in particular in amphibians. In this study, we investigated the relationships between winter, spring and summer NAO indexes and the long-term population dynamics of the plethodontid salamander Speleomantes strinatii. This terrestrial salamander was monitored inside an artificial cave in NW Italy for 24 consecutive years. The relationships between seasonal NAO indexes and the salamander dynamics were assessed by cross-correlation function (CCF) analysis, after prewhitening the time series by autoregressive moving average statistical modelling. Results of CCF analyses indicated that the salamander abundance varied in relation to the one-year ahead winter NAO (P = 0.018), while no relationships were found with spring and summer indexes. These results strengthen some previous findings that suggested a high sensitivity of temperate terrestrial amphibians to wintertime climatic conditions.

General method for the preparation of active esters by palladium-catalyzed alkoxycarbonylation of aryl bromides.

A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.

Heart rate variability and cardiovascular risk factors in adolescent boys.

OBJECTIVE: To establish reference values of heart rate variability (HRV) measures in a cohort of adolescent boys and to determine the relationship between HRV and the clustering of risk factors (RFs) for cardiovascular disease. STUDY DESIGN: This cross-sectional study included 1152 adolescent boys (age: 16.6 ± 1.2 years old). Demographic data, health-related habits, obesity indicators, and blood pressure were evaluated. HRV measures of time (SD of all RR intervals, root mean square of the squared differences between adjacent normal RR intervals, and the percentage of adjacent intervals over 50 ms) and frequency domains were assessed (low [LF] and high [HF] frequency). RESULTS: The components of HRV were RR interval (827 ± 128 ms), SD of all RR intervals (61.9 ± 23.5 ms), root mean square of the squared differences between adjacent normal RR intervals (54.5 ± 29.4 ms), percentage of adjacent intervals over 50 ms (29.4 ± 20.4%), LF (53 ± 16 nu), HF (47 ± 16), and LF/HF (1.44 ± 1.08). Greater sympathetic and lower parasympathetic modulation at rest were associated with higher adiposity, higher blood pressure and physical inactivity. Adolescents with 2 or more RFs also presented lower HRV than subjects with no RFs (P < .001). CONCLUSIONS: The study has provided descriptive indicators that help the interpretation of HRV results in adolescents. Lower HRV measures are associated with the clustering of cardiovascular RFs.

Antifungal and cytotoxic 2-acylcyclohexane-1,3-diones from Peperomia alata and P. trineura.

Bioactivity-guided fractionation of the separate CH2Cl2 extracts from the aerial parts of Peperomia alata and P. trineura yielded seven polyketides: alatanone A [3-hydroxy-2-(5'-phenylpent-4'E-enoyl)cyclohex-2-en-1-one, 1a] and alatanone B [3-hydroxy-2-(3'-phenyl-6'-methylenedioxypropanoyl)cyclohex-2-en-1-one, 2a] from P. alata and trineurone A [3-hydroxy-2-(11'-phenylundec-10'E-enoyl)cyclohex-2-en-1-one, 1b], trineurone B [3-hydroxy-2-(15'-phenyl-18'-methylenedioxypentadecanoyl)cyclohex-2-en-1-one, 2b], trineurone C [3-hydroxy-2-(17'-phenyl-20'-methylenedioxyheptadecanoyl)cyclohex-2-en-1-one, 2c], trineurone D [3-hydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3a], and trineurone E [(6R)-(+)-3,6-dihydroxy-2-(hexadec-10'Z-enoyl)cyclohex-2-en-1-one, 3b] from P. trineura. The isolated compounds were evaluated for antifungal activity against Cladosporium cladosporioides and C. sphaeospermum and for cytotoxicity against the K562 and Nalm-6 leukemia cell lines.

Exaggerating, mislabeling or simulating obsessive-compulsive symptoms: case reports of patients claiming to have obsessive-compulsive disorder.

BACKGROUND: There are no reported cases of factitious or simulated obsessive-compulsive disorder (OCD). However, over the last years, our clinic has come across a number of individuals that seem to exaggerate, mislabel or even intentionally "produce" obsessive and/or compulsive symptoms in order to be diagnosed with OCD. METHODS: In this study, experienced clinicians working on a university-based OCD clinic were requested to provide clinical vignettes of patients who, despite having a formal diagnosis of OCD, were felt to display non-genuine forms of this condition. RESULTS: Ten non-consecutive patients with a self-proclaimed diagnosis of OCD were identified and described. Although patients were diagnosed with OCD according to various structured interviews, they exhibited diverse combinations of the following features: (i) overly technical and/or doctrinaire description of their symptoms, (ii) mounting irritability, as the interviewer attempts to unveil the underlying nature of these descriptions; (iii) marked shifts in symptom patterns and disease course; (iv) an affirmative "yes" pattern of response to interview questions; (v) multiple Axis I psychiatric disorders; (vi) cluster B features; (vii) an erratic pattern of treatment response; and (viii) excessive or contradictory drug-related side effects. CONCLUSIONS: In sum, reliance on overly structured assessments conducted by insufficiently trained or naïve personnel may result in invalid OCD diagnoses, particularly those that leave no room for clinical judgment.

The association between cardiovascular risk factors and high blood pressure in adolescents: a school-based study.

OBJECTIVE: Although previous studies have analyzed the association between cardiovascular risk factors and blood pressure in adolescents, few studies conducted in developing countries analyzed whether the aggregation of risk factors contributes to an increased risk of high blood pressure in adolescents. The objective of this study was to assess the association between cardiovascular risk factors (including general overweight, abdominal obesity, high consumption of foods rich in fats, and insufficient physical activity levels) and high blood pressure in adolescents. METHODS: This study was carried out from 2007 to 2008 with 1021 adolescents (528 girls) from primary schools located in the city of Londrina- Brazil. Blood pressure was assessed using an oscillometric device. General overweight was obtained through body mass index, abdominal obesity was assessed using waist circumference, and the consumption of foods rich in fat and physical activity were assessed using a questionnaire. The sum of these risk factors was determined. RESULTS: Adolescents with three or four aggregated risk factors were more likely to have higher values of systolic and diastolic blood pressure when compared with adolescents who did not have any cardiovascular risk factors (P = 0.001 for both). Logistic regression indicated that groups of adolescents with 2 (OR= 2.46 [1.11-5.42]; P = 0.026), 3 (OR= 4.97 [2.07-11.92]; P = 0.001) or 4 risk factors (OR= 6.79 [2.24-19.9]; P = 0.001) presented an increased likelihood of high blood pressure. CONCLUSIONS: The number of cardiovascular risk factors was found to be related to high blood pressure in adolescents.

Perceived environmental characteristics and psychosocial factors associated with physical activity levels in adolescents from Northeast Brazil: structural equation modelling analysis.

This study aimed to investigate the direct and indirect associations between perceived environmental characteristics and psychosocial factors and physical activity levels in adolescents from Northeast Brazil. The sample was composed of 2,361 adolescents aged 14-19 years (56.6% female). Physical activity was measured using a questionnaire and environmental (perceived environmental characteristics) and psychosocial (self-efficacy, social support from parents and friends for physical activity) factors with previously validated scales. Perceived environmental characteristics were not directly associated with the levels of physical activity, but exhibited significant indirect associations, mediated by self-efficacy in males. Self-efficacy and social support were positively and directly associated with physical activity levels, and part of the associations between social support and physical activity was mediated by self-efficacy. Perception of self-efficacy and social support, important factors associated with physical activity levels in adolescents, should be the target of interventions aimed at increasing physical activity. Favorable environments for physical activity also need to be considered, since they have a positive influence on the self-efficacy of adolescents.

Clustering of 24H movement behaviors associated with clinic blood pressure in older adults: a cross-sectional study.

Physical activity (PA), sedentary behavior (SB), and sleep duration are known to have an individual effect on clinic blood pressure (BP) of older adults. However, whether different patterns of these so-called movement behaviors over the 24h-cycle on BP remains poorly investigated. The study aimed to identify movement behavior patterns associated with clinic BP among older adults with chronic diseases. Cross-sectional study with 238 older adults (80.3% female; mean age 68.8 ± 6.6) with at least one chronic disease. PA, SB, and sleep duration were measured by a triaxial accelerometer. Clinic systolic BP (SBP) and diastolic BP (DBP) were obtained through an automated method following standard procedures. Non-hierarchical K-means cluster and linear regression modeling were employed to identify the clusters of movement behaviors and to examine the associations. Two clusters were identified [active and non-sedentary, n = 103 (i.e., sufficient sleep duration, higher LPA and MVPA, and lower SB) and sedentary and inactive, n = 135 (i.e., sufficient sleep duration, lower LPA and MVPA, and higher SB). Active and non-sedentary older adults presented lower systolic BP compared to sedentary and inactive ones, even after adjustments for sociodemographic and clinical characteristics (ß = 6.356; CI 95% from 0.932 to 11.779; P = 0.022). No associations were found for diastolic BP. In conclusion, higher PA and lower SB were associated with lower systolic BP in older adults with chronic diseases. However, sleep duration did not modify this association. Therefore, interventions focusing on concomitantly increasing PA levels and reducing SB should be the priority for controlling blood pressure.

The anti-mitotic drug griseofulvin induces apoptosis of human germ cell tumor cells through a connexin 43-dependent molecular mechanism.

Griseofulvin, a widely used antifungal antimitotic drug has been proposed as an anti-tumoral treatment by way of in vitro experiments. Recently, in vivo demonstration of griseofulvin efficacy against multiple myeloma in mice argues for its potential as therapeutics for cancer. Nevertheless, the molecular mechanisms by which griseofulvin disrupts cancerous cell progression are far from being understood. In the present study, we found that griseofulvin inhibits human germ cell tumor cell growth through activation of mitochondrial caspase pathway (caspase 9 and 3) leading to the activation of apoptosis rather than an alteration of cell proliferation. Strikingly, we demonstrated that griseofulvin triggered the expression level of connexin 43 (mRNA and protein), a well described tumor-suppressor gene, known to participate in apoptosis regulation. Consistently, together with microtubule instability, a mechanism classically associated with cell death in response to griseofulvin, we observed a disruption of connexin 43/tubulin association concomitant of an enhanced translocation of connexin 43, or an immunoreactive fragment of the protein, from the cytoplasm to the nucleus. Finally, by using siRNA approaches we demonstrated the requirement of connexin 43 in the apoptotic induction of griseofulvin on our tumor cell model. Altogether, these results described a new molecular mechanism connexin 43-dependent targeted by griseofulvin leading to apoptosis of human germ cell tumor cells.

Does self-reported physical activity associate with high blood pressure in adolescents when adiposity is adjusted for?

Studies show that both low physical activity (PA) and adiposity are associated with a higher risk of hypertension. However, the relationship between PA and blood pressure in adolescents is controversial and other studies have reported that no association was observed. Of particular interest is the evaluation of whether the association between PA and high blood pressure is independent of adiposity. A sample of 3764 Brazilian adolescents who attend high schools was selected using random cluster sampling. Data were collected using the Global School-based Student Health Survey, anthropometry, and blood pressure readings. The prevalence of high blood pressure was 14.6% (95% Confidence Interval (CI) 13.5-15.7), higher amongst males (20.0%; 95%CI 18.0-22.1) compared with females (10.9%; 95%CI 9.7-12.3). Sixty-six per cent of the adolescents were reported to be insufficiently active. The prevalence of high blood pressure was 12.8% (95%CI 11.0-14.7) amongst active compared with 15.4% (95%CI 14.0-16.9) amongst insufficiently active adolescents. The association between PA and high blood pressure was observed only amongst females after adjusting for waist circumference (odds ratio (OR) 1.67; 95%CI 1.21-2.31) and body mass index (OR 1.71; 95%CI 1.23-2.37). Notwithstanding levels of adiposity, higher PA levels are associated with a lower prevalence of high blood pressure amongst females, although not amongst males.

Delusional misidentification syndromes in obsessive-compulsive disorder.

Delusional misidentification syndromes (DMS) have been rarely reported in patients with conditions other than schizophrenia-related disorders, diffuse brain disease (dementia) and focal neurological illness. In this report, we describe DMS (i.e. Capgras and Fregoli syndromes) in two patients with severe and treatment resistant obsessive-compulsive disorder (OCD), one with paranoid personality disorder (PPD) and the other with a pervasive developmental disorder (PDD) not otherwise specified. While our findings highlight an interesting phenomenon (the occurrence of DMS in OCD), it is presently unclear whether this association is rare or underreported. Misidentification syndromes might be the ultimate result of a combination of obsessive fears and preexisting cognitive bias/deficits, such as mistrustfulness (in PPD) or poor theory of mind (in PDD).

Impaired Decision-Making Capacity in the Elderly King David (c. 1040-970 BCE): Was Hypothyroidism the Underlying Cause?

It has been suggested in the medical literature that in the last period of his life King David (c. 1040-970 BCE) suffered from dementia, osteoporosis, hyperparathyroidism, Parkinson's disease, autonomic neuropathy, major depression, and malignancy. The goal of this study was to identify, based on the "Succession Narrative (SN)," a historically objective section of the Old Testament, the clinical syndrome presented by King David and to determine whether an impaired decision making capacity may have been manipulated by his courtiers to influence his succession's politics. The "SN" indicates that besides forgetfulness and trouble in thinking, King David suffered from marked cold intolerance and sexual dysfunction. The symptom triad consisting of cognitive impairment, cold intolerance, and sexual dysfunction is more strongly suggestive of hypothyroidism than of any other diagnoses proposed in the medical literature so far. We hypothesized that hypothyroidism was the underlying cause of the elderly King David's clinical picture and that his sometimes troubled thinking was successfully manipulated by the courtiers to favor his son Solomon's accession to the throne, with profound historical consequences.

Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.

Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects. The best match between the experimental and theoretical nuclear magnetic resonance (NMR) profiles was used to assign the preferred conformer in solution, which was supported by the thermodynamic analysis. Among the 15 distinct AZM structures, conformer M14, having a short intramolecular C6-OH … N H-bond, is predicted to be dominant in water and dimethyl sulfoxide (DMSO) solutions. The results indicated that the X-ray structure backbone is mostly conserved in solution, showing that large flexible molecules with several possible conformations may assume a preferential spatial orientation in solution, which is the molecular structure that ultimately interacts with biological targets.

Exosome Liberation by Human Neutrophils under L-Amino Acid Oxidase of Calloselasma rhodostoma Venom Action.

L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 µg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO's ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.