Diabetes as risk factor to severity of dengue in naïve patients.

Background: Dengue cases can progress to severe ant life-threating forms particularly in subsequent heterologous infections. However, recent studies had explored additional risk factors, including underlying health conditions, even in individuals without prior exposure to dengue, notably, in patients with endothelial dysfunction and chronic inflammation. This study examines the link between diabetes and the development of severe dengue disease in dengue-naive patients during the 2019 dengue outbreak in São Jose do Rio Preto, Brazil. Methodology: We enrolled 529 laboratory-confirmed dengue cases, identified through DENV RT-PCR or NS1 antigen assays in a hospital cohort of acute febrile illness. Subsequently, we investigated the presence of anti-dengue and anti-Zika IgG antibodies. Samples testing positive for Zika were excluded from the analyses. Two groups were analyzed: naïve (DV-), and dengue history (DV+). Results: Initially, presence of diabetes and kidney disease, as well as being dengue-naive, were associated with a higher frequency of severe and potentially severe clinical outcomes. Multivariate analysis identified diabetes as a risk factor, while the presence of anti-dengue antibodies was considered protective. Analysis of dengue naïve samples, highlighted diabetes as an independent risk factor to severe forms of dengue disease. In DV+ patients, no condition was highlighted as a risk factor by univariate analysis or multivariate analysis. Conclusions: We investigated and confirmed diabetes as a risk factor for severe dengue disease in individuals without prior dengue or Zika exposure. Our conclusions raise significant concerns given diabetes' ever increasing global prevalence and its potential impact on patients with or previous dengue exposure. Summary: The simultaneous escalation of diabetes and dengue worldwide is striking. Notably, diabetes presents as a significant risk factor for severe dengue. This accentuates the necessity of diabetes control in dengue prevention, considering its widespread prevalence and influence on disease severity.

Remediation through the coordinated use of local rice husk residues for the selective adsorption of iron and nickel in real landfill leachate.

Herein, we demonstrate the prospects of tackling several environmental problems by transforming a local rice husk residue into an effective adsorbent, which was then applied for the treatment of real landfill leachate (LL). The study focused on establishing (i) the effect of simple washing on morphological aspects, (ii) evaluating target adsorption capacity for total iron (Fe) and nickel (Ni), (iii) determining regeneration and reuse potential of the adsorbent and (iv) complying to the requirements of worldwide legislations for reuse of treated LL wastewater. The adsorbent was prepared by employing a simple yet effective purification process that can be performed in situ. The LL was collected post-membrane treatment, and the characterizations revealed high concentrations of Fe, Ni, and organic matter content. The simple washing affected the crystallinity, resulting in structural alterations of the adsorbents, also increasing the porosity and specific surface. The adsorption process for Ni occurred naturally at pH 6, but adjusting the pH to 3 significantly improved removal efficiency and adsorption capacity for total Fe. The kinetics were accurately described by the pseudo-second-order model, while the Langmuir model provided a better fit for the isotherms. The adsorbent was stable for 5 reuses, and the metals adsorbed were recovered through basic leaching. The removal capacities achieved underscore the remarkable effectiveness of the process, ensuring the treated LL wastewater meets rigorous global environmental legislations for safe use in irrigation. Thus, by employing the compelling methods herein optimized it is possible to refer to the of solving three environmental problems at once.

Leveraging citizen science for monitoring urban forageable plants.

Urbanization brings forth social challenges in emerging countries such as Brazil, encompassing food scarcity, health deterioration, air pollution, and biodiversity loss. Despite this, urban areas like the city of São Paulo still boast ample green spaces, offering opportunities for nature appreciation and conservation, enhancing city resilience and livability. Citizen science is a collaborative endeavor between professional scientists and nonprofessional scientists in scientific research that may help to understand the dynamics of urban ecosystems. We believe citizen science has the potential to promote human and nature connection in urban areas and provide useful data on urban biodiversity.

Citizen science data on urban forageable plants: a case study in Brazil.

This paper presents two key data sets derived from the Pomar Urbano project. The first data set is a comprehensive catalog of edible fruit-bearing plant species, native or introduced to Brazil. The second data set, sourced from the iNaturalist platform, tracks the distribution and monitoring of these plants within urban landscapes across Brazil. The study includes data from the capitals of all 27 federative units of Brazil, focusing on the ten cities that contributed the most observations as of August 2023. The research emphasizes the significance of citizen science in urban biodiversity monitoring and its potential to contribute to various fields, including food and nutrition, creative industry, study of plant phenology, and machine learning applications. We expect the data sets presented in this paper to serve as resources for further studies in urban foraging, food security, cultural ecosystem services, and environmental sustainability.

TLC and HPLC methods for the determination of plumbagin for the diagnosis of poisoning by Plumbago scandens L.

Plumbago scandens L. (Plumbaginaceae) occurs in all regions of Brazil. It has been described as toxic to cattle and goats. Caustic lesions in the upper digestive tract characterize poisoning. P. scandens contains a naphthoquinone named plumbagin, which presents high cytotoxic activity. Plumbago auriculata Lam., a widely used ornamental plant, is considered potentially toxic, but there is limited data about its toxicity. This work aimed to validate analytical methodologies for determining the levels of plumbagin in samples of leaves, stems, and rumen content to be used as an auxiliary chemical marker in the laboratory diagnosis of intoxication. One methodology used thin layer chromatography (TLC), and another used high-performance liquid chromatography (HPLC). The presence of palisade grass (Urochloa brizantha (Hochst. ex A.Rich.) R.D.Webster), Guinea grass (Megathyrsus maximus (Jacq.) B.K.Simon & S.W.L.Jacobs), corn silage, and rumen content did not interfere with plumbagin in the two methodologies. The TLC methodology generates qualitative results but is simple to implement and has a low cost. The HPLC methodology showed a limit of detection (LOD) of 0.01 µg/mL and a limit of quantification (LOQ) of 0.05 µg/mL. Leaf and stem samples of P. scandens evaluated showed high levels of plumbagin (0.261 ± 0.087 % and 0.327 ± 0.055 %, respectively). In contrast, leaves of P. auriculata did not show detectable levels of the toxin, and some stem samples showed low levels (up to 0.000114 %). Thus, these methodologies can be used to confirm or rule out the consumption of P. scandens in rumen content from animals suspected of poisoning.

Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions.

PURPOSE: Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients' overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS. MATERIALS AND METHODS: IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS. RESULTS: Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B-like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor-positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS. CONCLUSION: NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

REAP+: A single preparation for rapid isolation of nuclei, cytoplasm, and mitochondria.

REAP+ is an enhanced version of the rapid, efficient, and practical (REAP) method designed for the isolation of nuclear fractions. This improved version, REAP+, enables fast and effective extraction of mitochondria, cytoplasm, and nuclei. The mechanical cell disruption process has been optimized to cerebral tissues, snap-frozen liver, and HT22 cells with remarkable fraction enrichment. REAP+ is well-suited for samples containing minimal protein quantities, such as mouse hippocampal slices. The method was validated by Western blot and marker enzyme activities, such as LDH and G6PDH for the cytoplasmic fraction and succinate dehydrogenase and cytochrome c oxidase for the mitochondrial fraction. One of the outstanding features of this method is its rapid execution, yielding fractions within 15 min, allowing for simultaneous preparation of multiple samples. In essence, REAP+ emerges as a swift, efficient, and practical technique for the concurrent isolation of nuclei, cytoplasm, and mitochondria from various cell types and tissues. The method would be suitable to study the multicompartment translocation of proteins, such as metabolic enzymes and transcription factors migrating from cytosol to the mitochondria and nuclei. Moreover, its compatibility with small samples, such as hippocampal slices, and its potential applicability to human biopsies, highlights the potential application in medical research.

ß-Caryophyllene Inhibits Oxaliplatin-Induced Peripheral Neuropathy in Mice: Role of Cannabinoid Type 2 Receptors, Oxidative Stress and Neuroinflammation.

Peripheral neuropathy is an important adverse effect caused by some chemotherapeutic agents, including oxaliplatin (OXA). OXA-induced peripheral neuropathy (OIPN) is a challenging condition due to diagnostic complexities and a lack of effective treatment. In this study, we investigated the antiallodynic effect of ß-caryophyllene (BCP), a cannabinoid type 2 (CB2) receptor agonist, in a mouse model of OIPN. BCP treatment inhibited OXA-induced mechanical and cold allodynia in both preventive and therapeutic drug treatment regimens. Experiments with the CB2 receptor agonist GW405833 confirmed the role of CB2 receptors in OIPN. The CB2 antagonist SR144528 abrogated the anti-nociceptive effect of BCP on mechanical allodynia, without impacting OXA-induced sensitivity to cold. BCP decreased neuroinflammation, as inferred from TNF, IL-1ß, IL-6, and IL-10 profiling, and also reduced ROS production, lipid peroxidation, and 4-hydroxynonenal protein adduct formation in the spinal cords of OXA-treated mice. BCP did not affect the antitumor response to OXA or its impact on blood cell counts, implying that the cytotoxicity of OXA was preserved. These results underscore BCP as a candidate drug for OIPN treatment via CB2 receptor-dependent mechanisms, and anti-inflammatory and antioxidant responses in the spinal cord.

Clinical Characterization of Respiratory Syncytial Virus Infection in Adults: A Neglected Disease?

Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.

Pedagogical practices developed with children through hospital classes: An integrative literature review.

OBJECTIVE: To analyze the evidence available in the literature on the pedagogical practices developed with children through hospital classes. METHOD: An integrative review was conducted on July 20, 2022, in Scopus, MEDLINE/PubMed, CINAHL, LILACS, Web of Science, ERIC, Educ@, and Scielo using the following descriptors in English, Portuguese, and Spanish, extracted from DECS/MeSH, CINAHL, Brased/INEP, and ERIC Thesaurus: "Child, Hospitalized", "Education, Special", "Education Department, Hospital", "Hospital Classroom", "Hospital Class", "Child Rearing", "Educational Practices", "Early Childhood Education", "Education", "Hospital Pedagogy", and "Hospital Special Class". No time restriction was applied. The EndNot Web reference manager and the Rayyan software were used to select studies, and later, the methodological rigor and level of evidence were assessed. RESULTS: The 22 articles described pedagogical practices, including ludic activities, individualized work, working with regular school content, stimulation activities, pedagogical and dialogic listening, learning based on the exchange of knowledge, video games, computational robotics, and theatrical performance. CONCLUSION: Although difficulties were identified in implementing pedagogical practices in the hospital, they were shown to allow educational continuity and clinical improvement of hospitalized children. IMPLICATIONS FOR PRACTICE: Studies on the educational process within the hospital setting can contribute to the development of public policies and the guarantee of the right to education for hospitalized children. DESCRIPTORS: Special education; Hospital education department; Hospitalized child; Child rearing; Teaching.

No Association Between Interleukin 6 and Inducible Nitric Oxide Synthase Polymorphisms and Dengue Infection: A Case-Control Study.

BACKGROUND: Dengue is a life-threatening disease. The factors that lead to severe cases are not completely understood. The host immune system is involved in the response to infections and plays an important role in dengue infection. IL-6 and iNOS are components of the immune system and genetic polymorphisms in these genes may be involved in dengue virus infection. The study aimed to investigate the association of genetic polymorphisms in the IL6 and iNOS genes and dengue. METHODS: We performed a case-control study using 60 dengue-infected individuals and 119 healthy controls. Polymorphisms in the IL6 (T15A) and iNOS (-1173CT) genes were amplified by Real-Time PCR. Statistical analyses were performed using BioEstat 5.0. RESULTS: We identified that the frequency of T/A genotype of IL6 was higher in dengue fever patients and C/T genotype of iNOS was higher in dengue hemorrhagic fever patients, however, no association was found between these polymorphisms and dengue. CONCLUSION: Polymorphisms in iNOS and IL6 were not associated with dengue infection.

Omics-based identification of an NRF2-related auranofin resistance signature in cancer: Insights into drug repurposing.

Auranofin is a thioredoxin reductase-1 inhibitor originally approved for the treatment of rheumatoid arthritis. Recently, auranofin has been repurposed as an anticancer drug, with pharmacological activity reported in multiple cancer types. In this study, we characterized transcriptional and genetic alterations associated with auranofin response in cancer. By integrating data from an auranofin cytotoxicity screen with transcriptome profiling of lung cancer cell lines, we identified an auranofin resistance signature comprising 29 genes, most of which are classical targets of the transcription factor NRF2, such as genes involved in glutathione metabolism (GCLC, GSR, SLC7A11) and thioredoxin system (TXN, TXNRD1). Pan-cancer analysis revealed that mutations in NRF2 pathway genes, namely KEAP1 and NFE2L2, are strongly associated with overexpression of the auranofin resistance gene set. By clustering cancer types based on auranofin resistance signature expression, hepatocellular carcinoma, and a subset of non-small cell lung cancer, head-neck squamous cell carcinoma, and esophageal cancer carrying NFE2L2/KEAP1 mutations were predicted resistant, whereas leukemia, lymphoma, and multiple myeloma were predicted sensitive to auranofin. Cell viability assays in a panel of 20 cancer cell lines confirmed the augmented sensitivity of hematological cancers to auranofin; an effect associated with dependence upon glutathione and decreased expression of NRF2 target genes involved in GSH synthesis and recycling (GCLC, GCLM and GSR) in these cancer types. In summary, the omics-based identification of sensitive/resistant cancers and genetic alterations associated with these phenotypes may guide an appropriate repurposing of auranofin in cancer therapy.

Development of a nutritional risk screening tool for cancer patients undergoing outpatient treatment.

INTRODUCTION: Malnutrition is a common reality in many hospitals, especially in cancer patients. In order to avoid its late diagnosis, there are screening instruments that help professionals detect nutritional risk early, thus avoiding further damage to the nutritional status. OBJECTIVE: To develop a nutritional screening tool for cancer patients undergoing outpatient treatment. MATERIAL AND METHODS: This cross-sectional, observational study was carried out in cancer patients assisted at an outpatient clinic for nutritional care. Data were collected from nutritional care records, including bioelectrical and body composition data (by electrical bioimpedance spectroscopy), anthropometry (adductor pollicis muscle thickness, circumferences, and body mass index), routine clinical biochemical tests, and dynamometry. Malnourished patients were identified through screening using the NRS-2002 method, and all participants were classified according to the GLIM criterion as the control group (no risk and no malnutrition) and the malnourished group. The logistic regression method was used to select the variables that were more sensitive to nutritional risk, thus composing the final screening instrument. RESULTS: The study sample consisted of 72 patients, 58% male, with a mean age of 63 years (±13.3). The malnourished group had a higher frequency of sarcopenia, worse Karnofsky Performance Status (KPS), and lower values for weight, adductor pollicis muscle thickness (APMT), body mass index (BMI), calf circumference (CC), dynamometry (HAND), and fat mass index (FMI) than the control group. After multivariate analyses and analysis of covariance, the final model was devised in the form of an equation containing two variables, which were more associated with malnutrition, the BMI and the KPS. CONCLUSION: The screening instrument developed in this study resulted in an equation for screening nutritional risk, which included the variables KPS and BMI with 84% assertiveness.

Multiple hepatic infarctions secondary to diabetic ketoacidosis: A case report.

BACKGROUND: Hepatic infarctions (HI) are ischemic events of the liver in which a disruption in the blood flow to the hepatocytes leads to focal ischemia and necrosis. Most HI are due to occlusive events in the liver's blood vessels, but non-occlusive HI may occur. They are associated with disruption of microvasculature, such as in diabetic ketoacidosis. While HI usually presents as peripheral lesions with clear borders, irregular nodular lesions may occur, indistinguishable from liver neoplasms and presenting a diagnostic challenge. CASE SUMMARY: We report a case of multiple extensive HI in a patient with poorly controlled diabetes mellitus, who first presented to the emergency room with diabetic ketoacidosis. He then developed jaundice, thrombocytopenia, and a marked elevation of serum aminotransferases. An ultrasound of the liver showed the presence of multiple irregular lesions. Further investigation with a computerized tomography scan confirmed the presence of multiple hypoattenuating nodules with irregular borders and heterogeneous appearance. These lesions were considered highly suggestive of a primary neoplasm of the liver. While the patient was clinically stable, his bilirubin levels remained persistently elevated, and he underwent an ultrasound-guided percutaneous biopsy of the largest lesion. Biopsy results revealed extensive ischemic necrosis of hepatocytes, with no signs of associated malignancy. Three months after the symptoms, the patient showed great improvement in all clinical and laboratory parameters and extensive regression of the lesions on imaging exams. CONCLUSION: This case highlights that diabetic ketoacidosis can cause non-occlusive HI, possibly presenting as nodular lesions indistinguishable from neoplasms.

Reduced Prevalence of Measles Antibodies in a Cohort of Brazilian Children under 15 Years of Age.

Measles is a highly contagious acute febrile disease responsible for sporadic but explosive outbreaks worldwide. Although it was considered eliminated from the Americas, the disease reemerged in 2017. This reemergence was linked to reduced immunization rates. Vaccination, early identification of cases, and blocking of the transmission chain are the most effective tools to combat measles, for which there is not a specific antiviral treatment. In this Brazilian prospective cross-sectional study, we investigated the prevalence of measles antibodies in children, a population vulnerable to significant morbidity and mortality from exposure to infection. Between December 2018 to November 2019, blood samples from 252 children were collected and assessed for the presence of measles-specific IgG antibodies and an overall prevalence of 75.8% was observed. We further stratified the cohort into age subgroups, none of which exhibited antibody presence levels above the herd immunity threshold of 94%. Moreover, the calculated number of secondary cases resulting from a case in any age group ranged from 3 to 4, demonstrating that even with partial vaccination coverage this disease is still concerning and highly transmissible. Despite global warnings about measles and previous efforts to combat the advance of the disease, data on antibody prevalence and vaccination coverage in several countries are still concerning and indicate that significant parts of the population could be affected. Seroprevalence studies like this one are important to highlight actual epidemiological conditions and emphasize the need for additional strategies to encourage immunization and avoid the potential impacts of measles, particularly in children who can be severely affected.

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology.

Pure human and canine mammary invasive micropapillary carcinoma is a rare malignant epithelial tumor accounting for 0.9 to 2% of all invasive mammary carcinomas and present a high rate of lymphatic invasion and metastasis, with unfavorable prognosis. Surgery and chemotherapy are standard treatments for almost all mammary cancer in both species, as well as hormonal and target therapies available for human patients. However, depending on the patient's clinical staging, satisfactory therapeutic results for invasive micropapillary carcinoma are a challenge due to its high capacity of invasion and metastasis. Cyclooxygenase-2 (COX-2) isoform is an important enzyme stimulated by cytokines, growth factors and oncogenes activation to synthetizes prostaglandins in inflammatory process. COX-2 overexpression is associated with angiogenesis and invasion and contributes to cancer development, disease progression, tumor recurrence and regional lymph node metastasis in human and canine mammary carcinomas. This enzyme can be targeted by non-steroidal anti-inflammatory drugs and its inhibition can reduce tumor growth and metastasis in several cancer types. Given the similarity between both species, the present study aims to elucidate the involvement of COX-2 mRNA and protein expression in canine (cIMPC) and human (hIMPC) pure invasive mammary micropapillary carcinoma, with clinicopathological and survival data. Twenty-nine cases of cIMPC and 17 cases of hIMPC were analyzed regarding histologic type, grade, age, tumor size, lymph node condition, extracapsular extension, inflammatory infiltrate and immunophenotype. When available, information on adjuvant treatment, recurrence, metastasis and overall survival were collected. The present study demonstrated COX-2 protein expression in 65.5% of cIMPC and 92.3% of hIMPC, and an association with more advanced histological grades in bitches and higher Ki67 in women. COX-2 mRNA expression was significantly higher in cIMPC than in hIMPC, and its expression was not associated with COX-2 protein expression in both species. COX-2 mRNA expression was associated with negative-ER hIMPC as well as higher Ki67. cIMPC demonstrated proportional early development, more regional metastasis, and a prevalence of negative estrogen receptor, than hIMPC. This is the first time COX-2 expression is associated with negative prognostic factors in both cIMPC and hIMPC, besides the overexpression of COX-2 protein in such unfavorable histological type, which suggests that COX-2 can act as a potential target in IMPC.

Arboviral Infections in Neurological Disorders in Hospitalized Patients in São José do Rio Preto, São Paulo, Brazil.

Arbovirus infections are increasingly important causes of disease, whose spectrum of neurological manifestations are not fully known. This study sought to retrospectively assess the incidence of arboviruses in cerebrospinal fluid samples of patients with neurological symptoms to inform diagnosis of central and peripheral nervous system disorders. A total of 255 cerebrospinal fluid (CSF) samples collected from January 2016 to December 2017 were tested for dengue virus (DENV 1-4), Zika virus (ZIKV), and Chikungunya virus (CHIKV) in addition to other neurotropic arboviruses of interest, using genetic and serologic assays. Of the 255 CSF samples analyzed, 3.53% (09/255) were positive for arboviruses presenting mainly as meningitis, encephalitis, and cerebrovascular events, of which ZIKV was detected in 2.74% (7/255), DENV in 0.78% (2/255), in addition to an identified ILHV infection that was described previously. All the cases were detected in adults aged 18 to 74 years old. Our findings highlight the scientific and clinical importance of neurological syndromes associated with arboviruses and demonstrate the relevance of specific laboratory methods to achieve accurate diagnoses as well as highlight the true dimension of these diseases to ultimately improve public health planning and medical case management.

Pycard and BC017158 Candidate Genes of Irm1 Locus Modulate Inflammasome Activation for IL-1ß Production.

We identified Pycard and BC017158 genes as putative effectors of the Quantitative Trait locus (QTL) that we mapped at distal chromosome 7 named Irm1 for Inflammatory response modulator 1, controlling acute inflammatory response (AIR) and the production of IL-1ß, dependent on the activation of the NLRP3 inflammasome. We obtained the mapping through genome-wide linkage analysis of Single Nucleotide Polymorphisms (SNPs) in a cross between High (AIRmax) and Low (AIRmin) responder mouse lines that we produced by several generations of bidirectional selection for Acute Inflammatory Response. A highly significant linkage signal (LOD score peak of 72) for ex vivo IL-1ß production limited a 4 Mbp interval to chromosome 7. Sequencing of the locus region revealed 14 SNPs between "High" and "Low" responders that narrowed the locus to a 420 Kb interval. Variants were detected in non-coding regions of Itgam, Rgs10 and BC017158 genes and at the first exon of Pycard gene, resulting in an E19K substitution in the protein ASC (apoptosis associated speck-like protein containing a CARD) an adaptor molecule in the inflammasome complex. Silencing of BC017158 inhibited IL1-ß production by stimulated macrophages and the E19K ASC mutation carried by AIRmin mice impaired the ex vivo IL-1ß response and the formation of ASC specks in stimulated cells. IL-1ß and ASC specks play major roles in inflammatory reactions and in inflammation-related diseases. Our results delineate a novel genetic factor and a molecular mechanism affecting the acute inflammatory response.

The Role of the IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) Polymorphisms of Impulsive and Aggressive Personality Traits in Cocaine/Crack Users.

Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. In addition, the relationship between these polymorphisms and Impulsivity and Aggression was determined. We found that the physical aggressiveness sub score was negatively correlated with the C allele of -819C/T polymorphism of the IL-10 (b = -0.14; p = 0.04). The T allele of the SNP -786T/C of the ENOS gene positively predicts traits of physical aggressiveness (b = 0.14; p = 0.04). The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.