Showing papers by "Universidade Estadual de Londrina published in 2020"

Predictors of in-hospital COVID-19 mortality: A comprehensive systematic review and meta-analysis exploring differences by age, sex and health conditions.

Abstract: Objective Risk factors for in-hospital mortality in confirmed COVID-19 patients have been summarized in numerous meta-analyses, but it is still unclear whether they vary according to the age, sex and health conditions of the studied populations. This study explored these variables as potential mortality predictors. Methods A systematic review was conducted by searching the MEDLINE, Scopus, and Web of Science databases of studies available through July 27, 2020. The pooled risk was estimated with the odds ratio (p-OR) or effect size (p-ES) obtained through random-effects meta-analyses. Subgroup analyses and meta-regression were applied to explore differences by age, sex and health conditions. The MOOSE guidelines were strictly followed. Results The meta-analysis included 60 studies, with a total of 51,225 patients (12,458 [24.3%] deaths) from hospitals in 13 countries. A higher in-hospital mortality risk was found for dyspnoea (p-OR = 2.5), smoking (p-OR = 1.6) and several comorbidities (p-OR range: 1.8 to 4.7) and laboratory parameters (p-ES range: 0.3 to -2.6). Age was the main source of heterogeneity, followed by sex and health condition. The following predictors were more markedly associated with mortality in studies with patients with a mean age ≤60 years: dyspnoea (p-OR = 4.3), smoking (p-OR = 2.8), kidney disease (p-OR = 3.8), hypertension (p-OR = 3.7), malignancy (p-OR = 3.7), diabetes (p-OR = 3.2), pulmonary disease (p-OR = 3.1), decreased platelet count (p-ES = -1.7), decreased haemoglobin concentration (p-ES = -0.6), increased creatinine (p-ES = 2.4), increased interleukin-6 (p-ES = 2.4) and increased cardiac troponin I (p-ES = 0.7). On the other hand, in addition to comorbidities, the most important mortality predictors in studies with older patients were albumin (p-ES = -3.1), total bilirubin (p-ES = 0.7), AST (p-ES = 1.8), ALT (p-ES = 0.4), urea nitrogen (p-ES), C-reactive protein (p-ES = 2.7), LDH (p-ES = 2.4) and ferritin (p-ES = 1.7). Obesity was associated with increased mortality only in studies with fewer chronic or critical patients (p-OR = 1.8). Conclusion The prognostic effect of clinical conditions on COVID-19 mortality vary substantially according to the mean age of patients. PROSPERO registration number CRD42020176595.

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.

Abstract: Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

Double Chooz $\theta_{13}$ measurement via total neutron capture detection

Abstract: Neutrinos were assumed to be massless particles until the discovery of the neutrino oscillation process. This phenomenon indicates that the neutrinos have non-zero masses and the mass eigenstates (ν1, ν2, ν3) are mixtures of their flavour eigenstates (νe, νμ, ντ). The oscillations between different flavour eigenstates are described by three mixing angles (θ12, θ23, θ13), two differences of the squared neutrino masses of the ν2/ν1 and ν3/ν1 pairs and a charge conjugation parity symmetry violating phase δCP. The Double Chooz experiment, located near the Chooz Electricite de France reactors, measures the oscillation parameter θ13 using reactor neutrinos. Here, the Double Chooz collaboration reports the measurement of the mixing angle θ13 with the new total neutron capture detection technique from the full data set, yielding sin2(2θ13) = 0.105 ± 0.014. This measurement exploits the multidetector configuration, the isoflux baseline and data recorded when the reactors were switched off. In addition to the neutrino mixing angle measurement, Double Chooz provides a precise measurement of the reactor neutrino flux, given by the mean cross-section per fission 〈σf〉 = (5.71 ± 0.06) × 10−43 cm2 per fission, and reports an empirical model of the distortion in the reactor neutrino spectrum.

Diagnosis, prevalence, and clinical impact of sarcopenia in COPD: a systematic review and meta-analysis.

Abstract: Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria. This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD. This review was registered in PROSPERO (CRD42018092576). Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD. Study quality was assessed using validated instruments matched to study designs. Sarcopenia prevalence was determined using authors' definitions. Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality. Twenty-three studies (70% cross-sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men). Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies. Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538). People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference -7.1%; 95%CI -9.0 to -5.1%) and poorer exercise tolerance (standardized mean difference -0.8; 95%CI -1.4 to -0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all). No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers. Incident mortality was unreported in the literature. Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes. Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group.

Ensino superior em tempos de pandemia: diretrizes à gestão universitária

Abstract: RESUMO Instituicoes de Ensino Superior de todo o mundo foram afetadas pela pandemia da Covid-19. O prolongamento das medidas de distanciamento fisico entre pessoas impoe a adaptacao do ensino presencial ao formato remoto. Isso exige planejamento e consideracao as condicoes de estudantes e professores. Neste artigo, sao propostas diretrizes para orientar o trabalho de gestores universitarios ao avaliarem as dificuldades e limitacoes impostas pela situacao emergencial decorrente da pandemia, bem como lidarem com elas, de maneira a promover condicoes de trabalho e pedagogicas, viaveis e seguras, a professores e estudantes. Tais diretrizes sao baseadas em uma concepcao de Ensino Superior orientada para o desenvolvimento da capacidade de atuacao profissional (em oposicao a transmissao de conteudo). Sao tambem baseadas em variaveis que interferem no processo educacional.

Cytotoxicity and Antibacterial Activity of Alginate Hydrogel Containing Nitric Oxide Donor and Silver Nanoparticles for Topical Applications.

Abstract: Nitric oxide (NO) and silver nanoparticles (AgNPs) are well-known for their antibacterial activity. In this work, S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), a NO donor, and green tea synthesized AgNPs were individually or simultaneously incorporated into alginate hydrogel for topical antibacterial applications. The obtained hydrogels were characterized and the NO release and diffusion of AgNPs and S-nitroso-MSA from alginate hydrogels were investigated. The hydrogels showed a concentration dependent toxicity toward Vero cells. The potent antibacterial effect of the hydrogels was demonstrated toward Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Streptococcus mutans UA159. Interestingly, the combination of S-nitroso-MSA and AgNPs into alginate hydrogels had a superior antibacterial effect, compared with hydrogels containing S-nitroso-MSA or AgNPs individually. This is the first report to describe the synthesis, cytotoxicity, and antibacterial effects of alginate hydrogel containing NO donor and AgNPs. These hydrogels might find important local applications in the combat of bacterial infections.

Long Short-Term Memory and Fuzzy Logic for Anomaly Detection and Mitigation in Software-Defined Network Environment

Abstract: Computer networks become complex and dynamic structures. As a result of this fact, the configuration and the managing of this whole structure is a challenging activity. Software-Defined Networks(SDN) is a new network paradigm that, through an abstraction of network plans, seeks to separate the control plane and data plane, and tends as an objective to overcome the limitations in terms of network infrastructure configuration. As in the traditional network environment, the SDN environment is also liable to security vulnerabilities. This work presents a system of detection and mitigation of Distributed Denial of Service (DDoS) attacks and Portscan attacks in SDN environments (LSTM-FUZZY). The LSTM-FUZZY system presented in this work has three distinct phases: characterization, anomaly detection, and mitigation. The system was tested in two scenarios. In the first scenario, we applied IP flows collected from the SDN Floodlight controllers through emulation on Mininet. On the other hand, in the second scenario, the CICDDoS 2019 dataset was applied. The results gained show that the efficiency of the system to assist in network management, detect and mitigate the occurrence of the attacks.

The effect of silver nanoparticles on antioxidant/pro-oxidant balance in a murine model

Abstract: This study aimed to evaluate the subacute effect of two types of Ag-NPs(EG-AgNPs and PVP-EG-AgNPs) on antioxidant/pro-oxidant balance in rats. Seventy Wistar rats (35 males and 35 females) were divided in 7 groups and intraperitoneally exposed for 28 days to 0, 1, 2 and 4 mg/kg bw/day EG-Ag-NPs and 1, 2 and 4 mg/kg bw/day PVP- EG-Ag-NPs. After 28 days, the blood was collected, and the total antioxidant capacity (TAC), thiobarbituric reactive species (TBARS),protein carbonyl (PROTC) levels, reduced glutathione (GSH) levels and catalase (CAT) activity were determined. EG-Ag-NPs determined protective antioxidant effects in a dose-dependent manner. The exposure to the 4 mg/kg bw/day EG-Ag-NPs determines both in males and females a significant increase in TAC and CAT and a significant decrease in TBARS and PROTC only in females. The PVP-EG-AgNPs showed a different trend compared to EG-AgNPs. At 4 mg/kg bw/day the PVP-EG-AgNPs induce increased PROTC levels and decreased GSH (males and females) and TAC levels (males). The different mechanisms of EG-AgNPs and PVP-EG-AgNPs on antioxidant-/pro-oxidant balance can be explained by the influence of coating agent used for the preparation of the nanoparticles in the formation and composition of protein corona that influence their pathophysiology in the organism.

Effects of copper oxide nanoparticles on growth of lettuce (Lactuca sativa L.) seedlings and possible implications of nitric oxide in their antioxidative defense

Abstract: Copper oxide nanoparticles (CuO NPs) have been extensively explored for use in agriculture. Previous studies have indicated that application of CuO NPs might be promising for development and conservation of plants, pest control, and for the recovery of degraded soils. However, depending on the applied concentration copper can cause phytotoxic effects. In this work, biosynthesized CuO NPs (using green tea extract) were evaluated on their effects on lettuce (Lactuca sativa L.) seedling growth, which were exposed at concentrations ranged between 0.2 and 300 μg mL−1. From the biosynthesized were obtained ultra-small CuO NPs (~ 6.6 nm), with high stability in aqueous suspension. Toxicity bioassays have shown that at low concentrations (up to 40 μg mL−1), CuO NPs did not affect or even enhanced the seed germination. At higher concentrations (higher than 40 μg mL−1), inhibition of seed germination and radicle growth ranging from 35 to 75% was observed. With the increase of CuO NPs concentrations, nitrite and S-nitrosothiols levels in radicles increased, whereas superoxide dismutase and total antioxidant activities decreased. The nitrite and S-nitrosothiols levels in lettuce radicles showed a direct dose response to CuO NP application, which may indicate nitric oxide-dependent signaling pathways in the plant responses. Therefore, the results demonstrated that at low concentrations (≤ 20 μg mL−1) of CuO NPs, beneficial effects are obtained from seedlings, enhancing plant growth, and the involvement of nitric oxide signaling in the phytotoxic effects induced by high concentration of this formulation.

Prevalence, damage, management and insecticide resistance of stink bug populations (Hemiptera: Pentatomidae) in commodity crops

Abstract: Pest management of stink bugs (Hemiptera: Pentatomidae) in soybean [Glycine max (L.) Merr.], corn (Zea mays L.) and cotton (Gossypium spp.) agroecosystems has become a major concern in several countries of the Americas. In this review, we report an overview on geographical distribution, injury, damage and methods used to control (plant resistance mechanisms, biological control) the most important stink bugs in the Americas, with an emphasis on Brazil, the implications of the trend towards decreased susceptibility of stink bug populations to insecticides and the current difficulties of the management of these insect pests. Currently, the Neotropical brown stink bug Euschistus heros (Fabricius) is less susceptible to organophosphate insecticides than in the past. A slight reduction in E. heros susceptibility to pyrethroids and, to a lesser extent, to neonicotinoids has also been observed. In addition, the green‐belly stink bug [Dichelops melacanthus (Dallas)] is more tolerant to the three classes of insecticides (neonicotinoids, organophosphates and pyrethroids) than E. heros. Metabolic detoxification is involved in organophosphate, neonicotinoid and pyrethroid differences in susceptibility. Restricted availability of insecticides with different modes of action could favour the selection of resistant phenotypes in stink bug populations.

Microplastics and copper effects on the neotropical teleost Prochilodus lineatus: Is there any interaction?

Abstract: Microplastics (MP) are emerging contaminants widely found in aquatic ecosystems. In addition to MP toxicity itself, there is increasing concern about the MP adsorption capacity and the interactive effects with other contaminants, such as copper. The objective of this research was to investigate the effects of polyethylene microplastic and its association with copper (Cu) in genotoxic, biochemical, and physiological biomarkers of the neotropical teleost Prochilodus lineatus. Fish were exposed for 24 and 96 h to MP (20 μg L−1) and Cu (10 μg L−1) and MP + Cu. The results showed that MP and Cu, both isolated and in combination, promoted DNA damage in erythrocytes (96 h) and liver cells (24 and 96 h) indicating that MP and Cu are genotoxic. Fish exposed only to Cu (96 h) showed a decrease in lipid peroxidation in the liver despite of the decrease in glutathione content, indicating the efficiency of other antioxidant defenses. Brain acetylcholinesterase was inhibited in the animals from all the treatments. Although MP did not influence on Cu accumulation in tissues, decreased plasma Na+ and Ca2+ (24 h) occurred after the exposure to MP and Cu, isolated and combined. Exposure to MP and MP + Cu resulted in decreased activity of Ca2+-ATPase (24 h). Taken altogether, these results showed that MP and Cu depicted genotoxic, neurotoxic, and physiological effects on P. lineatus, both alone and combined. An interaction between Cu and MP was observed in plasma Ca2+, where the combination of both contaminants caused a greater effect than the contaminants alone.

Antenna Selection for Improving Energy Efficiency in XL-MIMO Systems

Abstract: We consider the recently proposed extra-large scale massive multiple-input multiple-output (XL-MIMO) systems, with some hundreds of antennas serving a smaller number of users. Since the array length is of the same order as the distance to the users, the long-term fading coefficients of a given user vary with the different antennas at the base station (BS). Thus, the signal transmitted by some antennas might reach the user with much more power than that transmitted by some others. From a green perspective, it is not effective to simultaneously activate hundreds or even thousands of antennas, since the power-hungry radio frequency (RF) chains of the active antennas increase significantly the total energy consumption. Besides, a larger number of selected antennas increases the power required by linear processing, such as precoding matrix computation, and short-term channel estimation. In this paper, we propose four antenna selection (AS) approaches to be deployed in XL-MIMO systems aiming at maximizing the total energy efficiency (EE). Besides, employing some simplifying assumptions, we derive a closed-form analytical expression for the EE of the XL-MIMO system, and propose a straightforward iterative method to determine the optimal number of selected antennas able to maximize it. The proposed AS schemes are based solely on long-term fading parameters, thus, the selected antennas set remains valid for a relatively large time/frequency intervals. Comparing the results, we find that the genetic-algorithm based AS scheme usually achieves the best EE performance, although our proposed highest normalized received power AS scheme also achieves very promising EE performance in a simple and straightforward way.

Changes in root morphological traits in soybean co-inoculated with Bradyrhizobium spp. and Azospirillum brasilense or treated with A. brasilense exudates

Abstract: We assessed the effects of co-inoculation with Azospirillum brasilense or the application of its exudates via seeds or leaf spray on root morphological traits and nodulation, as well as on shoot development and grain yield of soybean inoculated with Bradyrhizobium. Two experiments were performed in sterile substrate under greenhouse, and two were performed at field conditions in sandy soils in a crop season with episodes of drought. The treatments in the greenhouse experiments comprised the non-inoculated control, sole inoculation with Bradyrhizobium, co-inoculation of Bradyrhizobium and A. brasilense, and inoculation of Bradyrhizobium with the application of Azospirillum exudates via seeds or leaf spray. Field treatments included non-inoculated controls without and with N-fertilizer and inoculation of Bradyrhizobium and co-inoculation with A. brasilense. Plants were assessed for root weight, total and specific lengths, volume, diameter, tissue density, branches number, root-hair length and incidence, nodule number and dry weight, shoot dry weight and N content, and grain yield. Co-inoculation of Bradyrhizobium and A. brasilense and seed application of A. brasilense exudates increased the number of root branches and nodules compared with the sole inoculation of Bradyrhizobium. However, leaf spray application of exudates was less effective. Co-inoculation also increased specific root length, root length density in soil, root-hair incidence and length, and total N content in shoot, altogether resulting in increases in grain yield. Co-inoculation of soybean with Bradyrhizobium and A. brasilense improved several root morphological traits, increasing the plant capacity to overcome moderate drought stress episodes in sandy soils, allowing to reach higher yields.

Citric acid as crosslinking agent in starch/xanthan gum hydrogels produced by extrusion and thermopressing

Abstract: Biopolymers based hydrogels could have applications in various fields, such as packaging materials, drug delivery systems, biosensors, and agricultural practices. The current work aimed to develop starch/xanthan hydrogels through extrusion and thermopressing processes, using citric acid (CA) as crosslinking agent and sodium hypophosphite (SHP) as catalyst. The hydrogels were produced with different levels of CA (0.00, 0.75, 1.50 and 2.25 g/100 g polymer). Hydration, mechanical, thermal and microstructural properties of the hydrogels were determined. Swelling behavior of the materials with CA was lower than the control. Additionally, CA ensured the preservation of hydrogels integrity after the swelling process. Gel fraction increased with CA 0.75 g/100 g. Starch/xanthan hydrogels crosslinked with CA demonstrated lower strength than non-crosslinked hydrogels, which may be related to acid hydrolysis of the polymer chains. CA-SHP increased the storage modulus of the hydrogels. Reactive extrusion and thermopressing were efficient methods in the production of crosslinked starch/xanthan based hydrogels.

Atrazine nanoencapsulation improves pre-emergence herbicidal activity against Bidens pilosa without enhancing long-term residual effect on Glycine max.

Abstract: BACKGROUND: Poly(ϵ‐caprolactone) nanocapsules (NC + ATZ) are an efficient carrier system for atrazine and were developed as an alternative to reduce the harmful environmental effects of this herbicide. Here, we analyzed the pre‐emergence herbicidal activity of NC + ATZ against Bidens pilosa and evaluated its residual effect on soybean plants after different periods of soil treatment with the formulations. RESULTS: In contrast to non‐nanoatrazine, NC + ATZ treatment led to very high mortality rates of B. pilosa seedlings even after a tenfold dilution, which suggests that atrazine nanoencapsulation improved its pre‐emergence herbicidal activity. In a short‐term assay (17 days), soil treatment with all atrazine‐containing formulations resulted in intense toxicity to soybean plants. NC + ATZ at 200 g ha⁻¹ had the same inhibitory effects on the physiological and growth parameters of soybean plants compared with non‐nanoatrazine at 2000 g ha⁻¹, which suggests that atrazine nanoencapsulation increased the short‐term residual effect of the herbicide. In a long‐term assay (60 days), a gradual recovery of soybean plants from atrazine phytotoxicity was observed. When comparing the effects of nano‐ and non‐nanoatrazine at the same concentrations, the growth and physiological parameters of soybean plants were mainly affected to the same extent. This indicates that encapsulation of atrazine into poly(ϵ‐caprolactone) nanocapsules did not enhance the long‐term residual effect of the herbicide on soybean. CONCLUSION: NC + ATZ could be applied for efficient weed control without additional phytotoxicity to susceptible crops compared with non‐nanoatrazine, provided that a safe interval is respected from atrazine application to sowing. © 2019 Society of Chemical Industry

Effects of dietary supplementation with a microalga (Schizochytrium sp.) on the hemato-immunological, and intestinal histological parameters and gut microbiota of Nile tilapia in net cages

Abstract: Nutritional improvements in intensive aquaculture production systems is necessary for the reduction of stress, maximum utilization of nutritional components, and expression of the genetic potential of fish. The objective of this study was to evaluate the hemato-immunological, and histological parameters and gut microbiota of Nile tilapia fed with the microalga Schizochytrium sp. Males of Nile tilapia were distributed among eight net cages (6 m3), and fed for 105 days with two diets: control (CON), without Schizochytrium sp., and supplemented (SUP), with 1.2% Schizochytrium sp. in the diet. The final weight, mortality, hematocrit, total erythrocyte count (RBC), hemoglobin, hematimetric indices, white blood cell count (WBC), total protein, and serum lysozyme were measured. Alterations in intestinal morphology were evaluated. The gut microbiota was evaluated with next-generation sequencing. No significant differences (p>0.05) were found in the final weight and mortality between diets. Regarding the hematological parameters, a difference (p 0.05) in total protein and serum lysozyme concentrations or in WBCs between diets, except for lymphocytes, which presented lower values (p 0.05) in the intestinal morphology between diets. Metagenomic data indicated greater richness (represented by the Chao index) and a higher abundance of the bacterial phylum Firmicutes in the gut microbiota of the tilapia fed with the SUP diet, demonstrating that the digestion and use of the components of the microalga could influence the microbial community. The results indicated that the microalga had modulatory effects on blood cells and the intestinal microbiota, without affecting the structure and integrity of the intestinal villi.

Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: a Nomothetic Network Psychiatry Approach

Abstract: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: to compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (–SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, and total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n = 40) and non-deficit (n = 40) schizophrenia and healthy controls (n = 40). Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered –SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (odds ratio = 3.15, p < 0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, and IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas –SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. When overall severity of schizophrenia increases, multiple immune and oxidative (especially protein oxidation indicating chlorinative stress) neurotoxicities and impairments in immune-protective resilience become more prominent and shape a distinct nosological entity, namely deficit schizophrenia. The nomothetic network psychiatry approach allows building causal-pathway-phenotype models using machine learning techniques.