Coronary Artery Calcium Identified on Non-Gated Chest CT Scans: A Wasted Opportunity for Preventive Cardiological Care.

BACKGROUND: Coronary artery calcium (CAC) evaluated on dedicated cardiac computed tomography (CT) is an independent predictor of cardiovascular events. This study aimed to evaluate the correlation between CAC detected on non-gated standard chest CT and coronary lesions on coronary angiography (CAG) and determine its impact on prognosis. METHODS: Consecutive patients who underwent CAG due to acute coronary syndrome and had prior non-contrasted non-gated chest CT were included and retrospectively evaluated. Coronary artery calcium was evaluated by quantitative (Agatston score) and qualitative (visual assessment) assessment. RESULTS: A total of 114 patients were included in this study. The mean time difference between chest CT and CAG was 23 months. Coronary artery calcium was visually classified as mild, moderate, and severe in 31%, 33%, and 16% of patients, respectively. Moderate or severe CAC was an independent predictor of significant lesions on CAG (OR 22; 95% CI 8-61; p<0.001) and all-cause mortality (OR 4; 95% CI 2-9; p=0.001). Quantitative CAC evaluation accurately predicted significant lesions on CAG (AUC 0.81; p<0.001). While significant CAC was identified in 80% of chest CTs, formal reporting was 25%. CONCLUSION: Coronary artery calcium evaluation with chest CT was feasible and strongly associated with severity of coronary disease on CAG and mortality. Although the identification of CAC on chest CT represents a unique opportunity for cardiovascular risk stratification for preventive care, CAC underreporting is frequent.

Rabies in Bats (Chiroptera, Mammalia) in Brazil: Prevalence and Potential Risk Factors Based on Twenty Years of Research in the Northwestern Region of São Paulo, Brazil.

The number of rabies cases in bats has increased recently in Brazil and in the state of São Paulo, representing a new epidemiological scenario for this zoonosis. This study aimed to analyze the prevalence of rabies in bats according to food habits, taxonomic classification, sex and season of the year to identify possible risk factors for rabies occurrence in bats. A retrospective analysis of 6389 records of bat samples, from different municipalities of São Paulo, submitted to rabies diagnosis and taxonomic identification was carried out at the Rabies Diagnostic and Chiroptera Laboratories of Unesp Araçatuba, São Paulo, Brazil, from 1998 to 2017. Seventy-six (1.1%) positive rabies cases were detected in bats from ten species and seven genera of three families. The number of rabies-positive cases was higher in the dry season, with a significant association. The prevalence was higher in the Vespertilionidae family (37), especially Myotis nigricans (19) and Eptesicus furinalis (14). Frugivorous bats had a greater association with positivity for rabies, whereas the variable "sex" had no association. We recommend that the surveillance and control of rabies should be undertaken primarily during the dry season, especially in the Vespertilionidae family species and other species with a frugivorous food habit.

Gasdermin D pores are dynamically regulated by local phosphoinositide circuitry.

Gasdermin D forms large, ~21 nm diameter pores in the plasma membrane to drive the cell death program pyroptosis. These pores are thought to be permanently open, and the resultant osmotic imbalance is thought to be highly damaging. Yet some cells mitigate and survive pore formation, suggesting an undiscovered layer of regulation over the function of these pores. However, no methods exist to directly reveal these mechanistic details. Here, we combine optogenetic tools, live cell fluorescence biosensing, and electrophysiology to demonstrate that gasdermin pores display phosphoinositide-dependent dynamics. We quantify repeated and fast opening-closing of these pores on the tens of seconds timescale, visualize the dynamic pore geometry, and identify the signaling that controls dynamic pore activity. The identification of this circuit allows pharmacological tuning of pyroptosis and control of inflammatory cytokine release by living cells.

The effects of resistance training in patients with primary Sjogren's syndrome.

INTRODUCTION: Resistance training (RT) is well tolerated and has shown promise for decreasing fatigue. However, the effects of RT have never been examined in primary Sjogren's syndrome (pSS). OBJECTIVE: To assess the feasibility, effectiveness, and safety of a resistance exercise program on fatigue in patients with pSS. METHODS: This is a parallel, single-blind randomized trial. Women aged 18 years or older, diagnosed with pSS according to the American-European criteria, were included. We randomized 59 participants to a resistance training group (RT) or a control group (CG). Participants in the RT group performed a 16-week resistance exercise program. The sessions consisted of three sets of resistance exercises (10 repetitions each) at 60 to 80% of 1 repetition maximum, designed to improve whole-body strength. The participants in the CG received their usual pharmacological treatment and instructions regarding disease control, pain management, sleep hygiene, and activities of daily living. To compare intergroup and intragroup variability, a one-factor repeated-measures analysis of variance (ANOVA) was used. RESULTS: RT effectively improved fatigue, pain, functional capacity, emotional aspects, vitality, and subjective perception of disease activity by the patient. No between-group differences were found in the ESSPRI mental score, ESSDAI, SF-36-Physical Aspects, SF-36-General Health, SF-36-Social aspects, and SF-36-Mental Health after the training period. CONCLUSION: An RT program was safe and effective in improving fatigue, pain, functional capacity, emotional aspects, vitality, and subjective perception of disease activity by the patient in women with pSS. Key Points • This is the first study to evaluate the effects of a resistance training program on fatigue in patients with primary Sjogren's syndrome. • A resistance training program was shown to be effective in improving fatigue in patients with primary Sjogren's syndrome. • A resistance training program is well-tolerated, has good compliance, and is not associated with serious adverse effects in patients with primary Sjogren's syndrome.

Cardiovascular Effect of Physical Exercise on Primary Sjogren's Syndrome (pSS): Randomized Trial.

Objective: To evaluate the effects of an exercise program on aerobic capacity, echocardiographic parameters, metabolic profile, quality of life and safety in patients with primary Sjogren's syndrome in a randomized trial. Methods: 60 women with pSS were evaluated from the SF-36 Short-Form Health Survey (SF-36) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) questionnaires. The participants performed ergospirometry and echocardiography; blood samples were collected to evaluate the metabolic profile. Patients were randomly divided into 2 groups: a training group that participated in the supervised training program and a control group. All variables were analyzed at baseline and after 28 weeks for both groups and we performed an intention-to-treat analysis. The training program consisted of 16 weeks of resistance exercises and, after, the exercise became aerobic. Patients and coaches were not blinded, contrary to the evaluators of all examinations/procedures and data analysts. Statistical analysis included Wilcoxon's rank sum test, chi-square test, and ANOVA test. P values < 0.05 were considered to be statistically significant. Results: The 2 groups were homogeneous at baseline. The training group showed a significant improvement in oxygen maximum volume (VO2max) and anaerobic threshold (AT). Comparison of the training group and control group after 28 weeks showed a significant difference relating to VO2max and in AT. We did not find statistically significant diference in echocardiographic parameters, metabolic profile and in questionnaires SF-36 and ESSDAI. Conclusions: This study showed significant improvement in aerobic capacity and glycated hemoglobin after a supervised training program in patients with pSS with safety.

Follow-up of dairy cattle naturally infected by Trypanosoma vivax after treatment with isometamidium chloride.

Trypanosoma vivax infections cause nonspecific clinical signs in cattle associated with aparasitemic intervals, making disease diagnosis a challenge. In Brazil, diminazene aceturate and isometamidium chloride (ISM) are available to treat bovine trypanosomosis. The objective of this study was to follow-up, by molecular and serological techniques, dairy cattle naturally infected by T. vivax after ISM treatment. Thirty cattle naturally infected with T. vivax received two applications of ISM, at a dosage of 1.0 mg/kg intramuscularly, on days 0 and 150. For T. vivax diagnosis, EDTA-blood and serum samples were evaluated on 0, 7, 15, 30, 60, 90, 120, 150, 180, 210, and 240 days after treatment PCR, Loop-mediated isothermal amplification (LAMP) and ELISA. Animals with persistent detection of T. vivax DNA by both PCR and LAMP were found and continuous detection of anti-T. vivax IgG antibodies by ELISA, suggesting the presence of T. vivax resistance to ISM. The combination of LAMP and ELISA tests can prevent misdiagnosis of the parasite clearance in treated cattle, contributing to better disease control. This is the first experiment that demonstrates the persistence infection of T. vivax under ISM treatment in a natural infected herd and evidence of ISM chemotherapy-resistant T. vivax in Brazil.

Stage-specific protein regulation during somatic embryo development of Carica papaya L. 'Golden'.

Somatic embryogenesis is an important biotechnological technique for large-scale propagation of elite genotypes. Identifying stage-specific compounds associated with somatic embryo development can help elucidate the ontogenesis of Carica papaya L. somatic embryos and improve tissue culture protocols. To identify the stage-specific proteins that are present during the differentiation of C. papaya somatic embryos, proteomic analyses of embryos at the globular, heart, torpedo and cotyledonary developmental stages were performed. Mass spectrometry data have been deposited in the ProteomeXchange with the dataset identifier PXD021107. Comparative proteomic analyses revealed a total of 801 proteins, with 392 classified as differentially accumulated proteins in at least one of the developmental stages. The globular-staged presented a higher number of unique proteins (16), and 7 were isoforms of 60S ribosomal proteins, suggesting high translational activity at the beginning of somatic embryogenesis. Proteins related to mitochondrial metabolism accumulated to a high degree at the early developmental stages and then decreased with increasing development, and they contributed to cell homeostasis in early somatic embryos. A progressive increase in the accumulation of vicilin, late embryogenesis abundant proteins and chloroplastic proteins that lead to somatic embryo maturation was also observed. The differential accumulation of acetylornithine deacetylase and S-adenosylmethionine synthase 2 proteins was correlated with increases in putrescine and spermidine contents, which suggests that both polyamines should be tested to determine whether they increase the conversion rates of globular- to cotyledonary-staged somatic embryos. Taken together, the results showed that somatic embryo development in C. papaya is regulated by the differential accumulation of proteins, with ribosomal and mitochondrial proteins more abundant during the early somatic embryo stages and seed maturation proteins more abundant during the late stages.

Follow-up of dairy cattle naturally infected by Trypanosoma vivax after treatment with isometamidium chloride / Acompanhamento de bovinos leiteiros naturalmente infectados com Trypanosoma vivax após tratamento com cloreto de isometamidium

Abstract Trypanosoma vivax infections cause nonspecific clinical signs in cattle associated with aparasitemic intervals, making disease diagnosis a challenge. In Brazil, diminazene aceturate and isometamidium chloride (ISM) are available to treat bovine trypanosomosis. The objective of this study was to follow-up, by molecular and serological techniques, dairy cattle naturally infected by T. vivax after ISM treatment. Thirty cattle naturally infected with T. vivax received two applications of ISM, at a dosage of 1.0 mg/kg intramuscularly, on days 0 and 150. For T. vivax diagnosis, EDTA-blood and serum samples were evaluated on 0, 7, 15, 30, 60, 90, 120, 150, 180, 210, and 240 days after treatment PCR, Loop-mediated isothermal amplification (LAMP) and ELISA. Animals with persistent detection of T. vivax DNA by both PCR and LAMP were found and continuous detection of anti-T. vivax IgG antibodies by ELISA, suggesting the presence of T. vivax resistance to ISM. The combination of LAMP and ELISA tests can prevent misdiagnosis of the parasite clearance in treated cattle, contributing to better disease control. This is the first experiment that demonstrates the persistence infection of T. vivax under ISM treatment in a natural infected herd and evidence of ISM chemotherapy-resistant T. vivax in Brazil.

Resumo Em bovinos, infecções por Trypanosoma vivax geram sinais clínicos inespecíficos que, associados a intervalos aparasitêmicos, faz com que o diagnóstico da enfermidade seja desafiador. No Brasil, somente aceturato de diaminazeno e cloridrato de isometamidum (ISM) estão disponíveis para o tratamento da tripanossomose bovina. Este trabalho teve como objetivo acompanhar bovinos leiteiros naturalmente infectados por T. vivax, após o tratamento com ISM por meio de técnicas moleculares e sorológica. Foram utilizados 30 bovinos naturalmente infectados com T. vivax, sendo estes tratados com duas aplicações de ISM, na dosagem de 1,0 mg/kg por via intramuscular profunda, nos dias 0 e 150. Foram avaliadas, para diagnóstico de T. vivax, amostras de sangue acrescido de EDTA e soro, colhidas nos 0, 7, 15, 30, 60, 90, 120, 150, 180, 210 e 240 dias após os tratamentos pela reação em cadeia da polimerase (PCR), amplificação circular isotérmica do DNA (LAMP) e ensaio de imunoabsorção enzimático (ELISA). Verificou-se a presença de animais com persistência na detecção de DNA de T. vivax pela PCR e LAMP, bem como detecção contínua de anticorpos IgG anti-T. vivax pelo método de ELISA, sugerindo a presença de resistência de T. vivax ao ISM. A combinação dos testes LAMP e ELISA pode evitar falsos diagnósticos da eliminação do parasita nos bovinos tratados, contribuindo para um melhor controle da doença. Este é o primeiro experimento que demonstra infecção persistente do T. vivax em rebanho naturalmente infectado, tratado com ISM, e evidencia possível resistência ao quimioterápico no Brasil.

Correlation of sleep quality with fatigue and disease activity among patients with primary Sjögren's syndrome: a cross-sectional study.

BACKGROUND: Fatigue is a frequent symptom in patients with primary Sjögren's syndrome (pSS) and can be a cause of or be associated with sleep disorders. OBJECTIVE: To assess the sleep quality of pSS patients and its relationship with fatigue and disease activity. DESIGN AND SETTING: Analytical observational study conducted at an exercise psychobiology laboratory. METHODS: Sleep quality was evaluated using the Pittsburg sleep quality index (PSQI) and actigraphy. Fatigue was evaluated through the Profile of Fatigue and Discomfort - Sicca Symptoms Inventory (PROFAD-SSI-SF) and a visual analogue scale for fatigue (VAS-fatigue). Disease activity was evaluated using a visual analogue scale for pain (VAS-pain), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Disease Activity Index (ESSDAI). We summarized the data through descriptive statistics. RESULTS: A total of 50 female patients with pSS, of average age 56.4 years, were included in the study; 80% presented low disease activity. The total PSQI score showed that 74% had poor sleep. The actigraphy showed mean sleep latency of 26.2 minutes and mean nightly awakening of 48.2 minutes (duration of wakings after sleep onset, WASO). There were correlations between PSQI and VAS-pain, VAS-fatigue, PROFAD-SSI and ESSPRI. Actigraphy showed a correlation between the duration of WASO and ESSDAI. CONCLUSION: The present study provides important information regarding correlations between sleep disorders and disease activity. There is a need for proper control over disease activity and for development of strategies to help patients to sleep better in order to diminish their fatigue.

Correlation of sleep quality with fatigue and disease activity among patients with primary Sjögrens syndrome: a cross-sectional study

ABSTRACT BACKGROUND: Fatigue is a frequent symptom in patients with primary Sjögren's syndrome (pSS) and can be a cause of or be associated with sleep disorders. OBJECTIVE: To assess the sleep quality of pSS patients and its relationship with fatigue and disease activity. DESIGN AND SETTING: Analytical observational study conducted at an exercise psychobiology laboratory. METHODS: Sleep quality was evaluated using the Pittsburg sleep quality index (PSQI) and actigraphy. Fatigue was evaluated through the Profile of Fatigue and Discomfort - Sicca Symptoms Inventory (PROFAD-SSI-SF) and a visual analogue scale for fatigue (VAS-fatigue). Disease activity was evaluated using a visual analogue scale for pain (VAS-pain), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Disease Activity Index (ESSDAI). We summarized the data through descriptive statistics. RESULTS: A total of 50 female patients with pSS, of average age 56.4 years, were included in the study; 80% presented low disease activity. The total PSQI score showed that 74% had poor sleep. The actigraphy showed mean sleep latency of 26.2 minutes and mean nightly awakening of 48.2 minutes (duration of wakings after sleep onset, WASO). There were correlations between PSQI and VAS-pain, VAS-fatigue, PROFAD-SSI and ESSPRI. Actigraphy showed a correlation between the duration of WASO and ESSDAI. CONCLUSION: The present study provides important information regarding correlations between sleep disorders and disease activity. There is a need for proper control over disease activity and for development of strategies to help patients to sleep better in order to diminish their fatigue.

Pervasive Inter-Individual Variation in Allele-Specific Expression in Monozygotic Twins.

Despite being developed from one zygote, heterokaryotypic monozygotic (MZ) co-twins exhibit discordant karyotypes. Epigenomic studies in biological samples from heterokaryotypic MZ co-twins are of the most significant value for assessing the effects on gene- and allele-specific expression of an extranumerary chromosomal copy or structural chromosomal disparities in otherwise nearly identical germline genetic contributions. Here, we use RNA-Seq data from existing repositories to establish within-pair correlations for the breadth and magnitude of allele-specific expression (ASE) in heterokaryotypic MZ co-twins discordant for trisomy 21 and maternal 21q inheritance, as well as homokaryotypic co-twins. We show that there is a genome-wide disparity at ASE sites between the heterokaryotypic MZ co-twins. Although most of the disparity corresponds to changes in the magnitude of biallelic imbalance, ASE sites switching from either strictly monoallelic to biallelic imbalance or the reverse occur in few genes that are known or predicted to be imprinted, subject to X-chromosome inactivation or A-to-I(G) RNA edited. We also uncovered comparable ASE differences between homokaryotypic MZ twins. The extent of ASE discordance in MZ twins (2.7%) was about 10-fold lower than the expected between pairs of unrelated, non-twin males or females. The results indicate that the observed within-pair dissimilarities in breadth and magnitude of ASE sites in the heterokaryotypic MZ co-twins could not solely be attributable to the aneuploidy and the missing allelic heritability at 21q.

Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues.

A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC) of alleles at CpG islands (CGIs) in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion. iDMRs function as regulatory platforms, built through the recruitment of chemical modifications to histones to achieve differential, parent-of-origin-dependent chromatin segmentation states. Here, we used a comparative computational data mining approach to identify 125 novel constitutive candidate iDMRs that integrate the maximal number of allele-specific methylation region records overlapping CGIs in human methylomes. Twenty-nine candidate iDMRs display gametic 5mCpG asymmetry, and another 96 are candidate secondary iDMRs. We established the maternal origin of the 5mCpG imprints of one gametic (PARD6G-AS1) and one secondary (GCSAML) iDMRs. We also found a constitutively hemimethylated, nonimprinted domain at the PWWP2AP1 promoter CGI with oocyte-derived methylation asymmetry. Given that the 5mCpG level at the iDMRs is not a sufficient criterion to predict active or silent locus states and that iDMRs can regulate genes from a distance of more than 1 Mb, we used RNA-Seq experiments from the Genotype-Tissue Expression project and public archives to assess the transcriptional expression profiles of SNPs across 4.6 Mb spans around the novel maternal iDMRs. We showed that PARD6G-AS1 and GCSAML are expressed biallelically in multiple tissues. We found evidence of tissue-specific monoallelic expression of ZNF124 and OR2L13, located 363 kb upstream and 419 kb downstream, respectively, of the GCSAML iDMR. We hypothesize that the GCSAML iDMR regulates the tissue-specific, monoallelic expression of ZNF124 but not of OR2L13. We annotated the non-coding epigenomic marks in the two maternal iDMRs using data from the Roadmap Epigenomics project and showed that the PARD6G-AS1 and GCSAML iDMRs achieve contrasting activation and repression chromatin segmentations. Lastly, we found that the maternal 5mCpG imprints are perturbed in several hematopoietic cancers. We conclude that the maternal 5mCpG imprints at PARD6G-AS1 and GCSAML iDMRs are decoupled from parent-of-origin transcriptional expression effects in multiple tissues.

Asymptomatic Atherosclerosis in Primary Sjögren Syndrome: Correlation Between Low Ankle Brachial Index and Autoantibodies Positivity.

BACKGROUND: Primary Sjögren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjögren syndrome an interesting model for the study of atherosclerosis. OBJECTIVES: The aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjögren syndrome using noninvasive methods. METHODS: We assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjögren's Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI). RESULTS: Fifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjögren's Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor). CONCLUSIONS: The subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group.

Expression and purification of the recombinant SALT lectin from rice (Oryza sativa L.).

The SALT protein is a 14.5 kDa mannose-binding lectin, originally described as preferentially expressed in rice plant roots in response to NaCl stress. Recombinant SALT lectin was produced in Escherichia coli from a cDNA clone encoding protein. After isopropyl-beta-d-thiogalactopyranoside induction, the expression level achieved was 23% of the soluble protein. The recombinant agglutinin was purified by a single-step process by dialyses against a high concentrated salt solution. After purification, hemagglutination assays of rabbit erythrocytes revealed that the recombinant SALT protein is a potent agglutinin (0.078 microg ml(-1) minimal concentration). The purified recombinant lectin was also used for comparative estimation of native protein amounts in protein extracts from rice plants by Western blot assay.

Phytosecretion of enteropathogenic Escherichia coli pilin subunit A in transgenic tobacco and its suitability for early life vaccinology.

A plant expression cassette system was engineered to efficiently target proteins to the default secretory pathway, allowing the expression of DNA inserts in three frames as fusion proteins containing a synthetic tobacco calreticulin cleavable signal peptide sequence, with the advantage of producing the recombinant proteins by phytosecretion. As one approach to develop a vaccine to enteropathogenic Escherichia coli (EPEC) infection, the oral immunogenicity of phytosecreted BfpA, the structural subunit A of the bundle-forming pilus, expressed at high levels (7.7% of soluble protein) in transgenic tobacco tissues, was demonstrated in BALB/c mice by the induction and detection of fecal anti-BfpA antibodies.