Search

Trichomonas vaginaliscauses trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to studyT. vaginalisinfection response in a microorganism-free environment, an infection model was established providing a host–parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed onT. vaginalisclearance. Increased viability ofT. vaginaliswas observed when the NETs inhibitors, metformin and Cl−amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in anin vivointeraction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on theT. vaginalisviability.

The peptide, denominated Ct1a, is a β-toxin of 66 amino acids, isolated from venom of the scorpion, Centruroides tecomanus, collected in Colima, Mexico. This toxin was purified using size exclusion, cationic exchange, and reverse phase chromatography. It is the most abundant toxin, representing 1.7% of the soluble venom. Its molecular mass of 7588.9 Da was determined by mass spectrometry. The amino acid sequence was determined by Edman degradation and confirmed by transcriptomic analysis. Since neurons of the suprachiasmatic nucleus (SCN) maintain a spontaneous firing rate (SFR), we evaluated the physiological effects of toxin Ct1a on these neurons. The SFR exhibited a bimodal concentration-dependent response: 100 nM of Ct1a increased the SFR by 223%, whereas 500 nM and 1000 nM reduced it to 42% and 7%, respectively. Control experiments, consisting of recordings of the SFR during a time similar to that used in Ct1a testing, showed stability throughout the trials. Experiments carried out with denatured Ct1a toxin (500 nM) caused no variation in SFR recordings. Action potentials of SCN neurons, before and after Ct1a (100 nM) showed changes in the time constants of depolarization and repolarization phases, amplitude, and half-time. Finally, recordings of hNav1.6 sodium currents indicated that Ct1a shifts the channel activation to a more negative potential and reduces the amplitude of the peak current. These results all demonstrate that toxin Ct1a affects the SFR of SCN neurons by acting upon sodium channels of sub-type 1.6, implicating them in regulation of the SFR of SCN neurons.

Background: Heart failure is a leading cause of death worldwide and is associated with the rising prevalence of obesity, hypertension, and diabetes. O -GlcNAcylation (the attachment of O -linked β-N-acetylglucosamine [ O -GlcNAc] moieties to cytoplasmic, nuclear, and mitochondrial proteins) is a posttranslational modification of intracellular proteins and serves as a metabolic rheostat for cellular stress. Total levels of O -GlcNAcylation are determined by nutrient and metabolic flux, in addition to the net activity of 2 enzymes: O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA). Failing myocardium is marked by increased O -GlcNAcylation, but whether excessive O -GlcNAcylation contributes to cardiomyopathy and heart failure is unknown. Methods: We developed 2 new transgenic mouse models with myocardial overexpression of OGT and OGA to control O -GlcNAcylation independent of pathologic stress. Results: We found that OGT transgenic hearts showed increased O -GlcNAcylation and developed severe dilated cardiomyopathy, ventricular arrhythmias, and premature death. In contrast, OGA transgenic hearts had lower O -GlcNAcylation but identical cardiac function to wild-type littermate controls. OGA transgenic hearts were resistant to pathologic stress induced by pressure overload with attenuated myocardial O -GlcNAcylation levels after stress and decreased pathologic hypertrophy compared with wild-type controls. Interbreeding OGT with OGA transgenic mice rescued cardiomyopathy and premature death, despite persistent elevation of myocardial OGT. Transcriptomic and functional studies revealed disrupted mitochondrial energetics with impairment of complex I activity in hearts from OGT transgenic mice. Complex I activity was rescued by OGA transgenic interbreeding, suggesting an important role for mitochondrial complex I in O -GlcNAc–mediated cardiac pathology. Conclusions: Our data provide evidence that excessive O -GlcNAcylation causes cardiomyopathy, at least in part, attributable to defective energetics. Enhanced OGA activity is well tolerated and attenuation of O -GlcNAcylation is beneficial against pressure overload–induced pathologic remodeling and heart failure. These findings suggest that attenuation of excessive O -GlcNAcylation may represent a novel therapeutic approach for cardiomyopathy.

INTRODUCTION The present case describes the treatment of a mucoepidermoid carcinoma in a 13-year-old female sterilized European domestic cat, using lung lobectomy and -accompanying mitoxantrone chemotherapy. Six, 14, 19 and 27 months after the initial treatment tomodensitometric and radiographic examinations showed no abnormalities. However, the cat had to be euthanized 27 months after the lung lobectomy due to a soft tissue sarcoma in the interscapular area.

Nevoid acanthosis nigricans is a rare, benign form of acanthosis nigricans. Of the 24 cases documented in the literature, only two are exclusively localized to the umbilicus. We present four cases of nevoid acanthosis nigricans localized to the umbilicus; in patients less than 25 years of age, with no known co-morbidities, three of whom were females. Two of the cases received, with good response, treatment based on topical calcipotriol, a medication not previously reported to be used for this indication. Contrary to other types of acanthosis nigricans, the nevoid acanthosis nigricans is not associated with any syndrome, endocrinopathy, obesity, medication, or neoplasia and it can be confused with other pathologies such as epidermal nevus or dermatosis neglecta.

Background: Established relationships be­tween researchers, stakeholders and poten­tial participants are integral for recruitment of potential older adult participants and Evidence-Based Programs (EBPs) for chronic disease management have empirically been shown to help improve health and maintain healthy and active lives. To accelerate recruitment in EBPs and potential future research, we propose a Wellness Pathway allowing for delivery within multipurpose senior centers (MPCs) linked with medical facilities among lower-income urban older adults. The study aims were to: 1) assess the effectiveness of three MPC-delivered EBPs on disease management skills, health outcomes, and self-efficacy; and 2) assess the feasibility of the proposed Wellness Pathway for lower-income urban-dwelling older adults of color. Methods: We administered surveys and conducted a pre-post analysis among participants enrolled in any 1 of 3 MPC-based EBPs (n=53). To assess feasibility of the pathway, we analyzed survey data and interviews (EBP participants, MPC staff, physicians, n=10). Results: EBP participation was associated with greater disease management skills (increased time spent stretching and aerobic activity) but not improvements in self-effica­cy or other health outcomes. Interviews re­vealed: 1) older adults valued EBPs and felt the Wellness Pathway feasible; 2) staff felt it feasible given adequate growth manage­ment; 3) physicians felt it feasible provided adequate medical facility integration. Conclusion: MPC-based EBPs were associ­ated with improvements in disease manage­ment skills among older adults; a proposed Wellness Pathway shows early evidence of feasibility and warrants further investigation. Future efforts to implement this model of recruiting older adults of color into EBPs should address barriers for implementation and sustainability. Ethn Dis . 2020;30(Suppl 2):735-744; doi:10.18865/ed.30.S2.735

Hispanic women in the United States are disproportionately affected by intimate partner violence (IPV). One correlate of IPV among Hispanic women with important public health implications is substance misuse. However, limited research has identified culturally relevant factors that may impact the strength of the IPV-substance misuse association in this population. The present study examined the moderating role of acculturation in the relation between IPV types (i.e., physical, psychological, and sexual) and substance (i.e., alcohol and drug) misuse. Participants were 150 IPV-exposed Hispanic women in the community ( M age = 35.13). IPV types, substance misuse outcomes, and acculturation were significantly and positively correlated with each other at zero-order. Moderation analyses indicated that the relations between IPV and substance misuse were stronger among Hispanic women with higher (vs. lower) levels of acculturation. These findings suggest the potential utility of considering acculturation when assessing and treating substance misuse among IPV-exposed Hispanic women.

PURPOSE: Biobanks usually do not collect transgender and gender-diverse (TGD) demographic information, hindering research on cancer risk and biological effects related to gender-affirming interventions. METHODS: In August 2019, 172 scientists involved in biobanking research at a single institution (H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL) were invited to complete a survey measuring knowledge and attitudes about TGD health and research practices. Quantitative and qualitative analyses were performed. RESULTS: Among 47 respondents, there was high agreement (77%) regarding the importance of collecting TGD identities and histories of gender-affirming treatments with biospecimens, which was contrasted by low self-reported rates of respondents’ biorepositories allowing for the entry of TGD identities (14.9%) and histories of gender-affirming interventions (8.5%). There was high interest in receiving education regarding the unique cancer health needs of TGD patients (74%), and knowledge questions yielded high percentages of “neutral” and “don’t know or prefer not to answer” responses. After completing the survey, confidence in knowledge of health needs for TGD patients decreased significantly (48.9% were confident during the presurvey assessment v 36.2% in the postsurvey assessment; P < .001). Qualitative analysis of open-ended questions indicated overall support of TGD data inclusion in biobanks along with perceived barriers to inclusion of such data in biobanks. CONCLUSION: To our knowledge, this was the first study of researchers to assess knowledge, attitudes, and research practices regarding TGD patients. Overall, there was limited knowledge about TGD health and cancer needs and low rates of TGD demographic data collection but a high interest in receiving education regarding this community.

We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported. To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit. Cap, Cit, and the co-administration of both substances were evaluated in a modified version of the FST (30-cm water depth) conducted in rats, as well as in the open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM). In line with previous studies, independent administration of Cap and Cit displayed antidepressant-like properties in the FST, while the combined injection had synergistic effects. In the OFT, neither treatment caused significant increments in locomotion. In the EPM, the time spent in the closed arms was lower in groups administered either only Cap or a combination of Cap and Cit than in groups treated with Cit alone. In the MWM, both Cap and the joint treatment (Cap and Cit) improved the working memory of rats in comparison with animals treated only with Cit. Combined administration of Cap and Cit produces a synergistic antidepressant-like effect in the FST and reduces the detrimental effects of Cit on anxiety and working memory.

Flavobacterium psychrophilum is the causative agent of bacterial cold-water disease and rainbow trout syndrome in freshwater salmonid fish worldwide, generating injuries and high mortality rates. Despite several studies on this bacterium, the infection mechanism remains unknown due to limitations in the employed animal models. In this work, we propose using zebrafish (Danio rerio) as a model for studying bacterial pathogenicity. To substantiate this proposal, zebrafish infection by F. psychrophilum strain JIP 02/86 was characterized. Zebrafish larvae were infected using the bath method, and morphological changes and innate immune system activation were monitored using transgenic fish. Salmonid-like infection phenotypes were observed in 4.74% of treated larvae, as manifested by fin, muscle and caudal peduncle damage. Symptomatic and dead larvae accounted for 1.35% of all challenged larvae. Interestingly, infected larvae with no infection phenotypes showed stronger innate immune system activation than specimens with phenotypes. A failure of function assay for myeloid factor pu.1 resulted in more infected larvae (up to 43.5%), suggesting that low infection rates by F. psychrophilum would be due to the protective actions of the innate immune system against this bacterium in zebrafish larvae. Our results support the use of zebrafish as an infection model for studying F. psychrophilum. Furthermore, the percentage of infected fish can be modulated by disturbing, to varying extents, the differentiation of myeloid cells. Using this evidence as a starting point, different aspects of the infection mechanism of F. psychrophilum could be studied in vivo.

Hispanic women in the United States experience disproportionate mental health impacts of intimate partner violence (IPV). Following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews guidelines, we synthesized the existing knowledge based on IPV and mental health outcomes among Hispanic women in the United States. In May 2020, we searched five electronic databases (i.e., MEDLINE, PILOTS, PSYCInfo, PSYCArticles, and EMBASE). From the initial 1,180 results, 13 articles met inclusion criteria for this review (written in English, empirical study, focus on the experiences of victimization from an intimate partner, focus on mental health outcomes occurring in the person experiencing IPV, included women who identify as Hispanic, and included participants residing in the United States), representing 4,060 women. Findings highlighted significant positive associations between IPV ( n = 13; 4,060 women) and general mental health outcomes ( n = 4; 759 women) as well as the specific outcomes of depression ( n = 12; 2,661 women), anxiety ( n = 1; 274 women), post-traumatic stress disorder ( n = 3; 515 women), and substance misuse ( n = 2; 1,673 women) among Hispanic women in the United States. Limitations included heterogeneity across Hispanic populations and methodological differences between studies. Key avenues for future research were identified, including the need to examine mental health outcomes understudied in relation to IPV among Hispanic women (e.g., personality, obsessive-compulsive, and eating disorders) and to identify cultural and demographic factors (e.g., nativity status, level of acculturation) that may influence relations between IPV and mental health outcomes among Hispanic women. Such research can inform prevention and intervention efforts aimed at improving mental health among Hispanic women in the Untied States experiencing IPV.

Antibodies against SARS-CoV-2 decay but persist six months post-vaccination, with lower levels of neutralizing titers against Delta than wild-type. Only 2 of 227 vaccinated healthcare workers experienced outpatient symptomatic breakthrough infections despite 59 of 227 exhibiting serological evidence of exposure to SARS-CoV-2 as defined by development of anti-nucleocapsid protein antibodies.

Background/Introduction Since patients with coronary ectasia have an increased risk of developing myocardial infarction and cardiovascular death, these patients could benefit from a more intensive treatment. Unfortunately, the evidence regarding outcomes with different management strategies is limited, especially with direct oral anticoagulants (DOAC). Purpose To compare clinical outcomes in patients with coronary ectasia based on the selected/chosen treatment strategy. Methods We conducted a retrospective cohort study in patients diagnosed with coronary artery ectasia. They were divided into 3 different groups based on the treatment they received at discharge and we evaluated the main cardiovascular outcomes at one-year follow-up. Results Between 2016 and 2019, 7,579 angiographies were performed, in which 510 patients with coronary ectasia were found (prevalence of 6.72%). Of these patients, 43.9% (n=224) had the diagnosis of STEMI, 21% NSTEMI (n=107), 5.1% unstable angina (n=26), 18.6% chronic stable angina (n=95) and other 11.4% (n=58). The angiographic distribution of the lesions was as follows: left main coronary artery 25.1%, Left descending coronary artery 62.7%, circumflex artery 52.1%, right coronary artery 79.2%. It was possible to obtain the follow-up of 363 patients (71.2%) because 25 died during their hospitalization and data of 122 were not available at the time of analysis. Three groups were formed based on the treatment: (1) Dual Antiplatelet Therapy (DAPT) in 47% (n=174); (2) DAPT + Vitamin K Antagonist (VKA) in 8.5% (n=31); (3) DAPT + DOAC in 6.6% (n=24). The overall MACE rate at 1-year of follow-up was 6.6% (n=15): 11 patients in the DAPT group (6.3%), 1 patient in the DAPT + VKA group (3.2%), and 3 patients in the DAPT + DOAC group (12.5%). During this period, 3 patients died from cardiovascular causes, all of them in the DAPT group. Myocardial infarction occurred in 12 patients, 8 in the DAPT group (4.2%), 1 in the DAPT + VKA group (3.2%) and 3 in the DAPT + DOAC group (12.5%). Stroke occurred in 2 patients: 1 patient in the DAPT group (0.5%) and 1 patient in the DAPT + DOAC group, 4.1% None of these findings were statistically significant. One-year occurrence of bleeding events was also evaluated: 23 patients presented a bleeding event, 14 in the DAPT group (8%), 7 in the DAPT + VKA group (22.5%) and 2 in the DAPT + DOAC group (8.3%); p=0.010. Conclusion(s) Our findings suggest that there is no statistically significant difference in the incidence of thrombotic complications, when comparing the treatment options. Patients using the combination of DAPT+VKA have a higher incidence of bleeding. Funding Acknowledgement Type of funding sources: None.

Resumen Antecedentes y objetivo En la posmenopausia se presentan alteraciones en el metabolismo de los lipidos, sensibilidad a la insulina e incremento del tejido adiposo visceral, lo que se asocia a un aumento del riesgo cardiometabolico. La osteocalcina (OCN) es una proteina de remodelacion osea, que recientemente se ha observado que participa en la regulacion del metabolismo de la glucosa, lipidos y del tejido adiposo. Son limitados los estudios de OCN en la etapa posmenopausica. El objetivo de este trabajo fue investigar la relacion de la concentracion de OCN con la obesidad y el sindrome metabolico (SM) en mujeres pre y posmenopausicas. Metodos Estudio transversal que incluyo a 261 participantes de 45 a 60 anos, quienes fueron evaluadas clinicamente y se les midio glucosa y perfil de lipidos. La OCN serica y la insulina se determinaron por quimioluminiscencia. Resultados De las participantes, 128 fueron premenopausicas y 133 posmenopausicas; el 33% de las participantes presentaban SM. En las mujeres posmenopausicas, la concentracion de OCN fue superior en comparacion a las premenopausicas (7,2 ± 4,0 vs. 5,5 ± 6,4 ng/mL, p Conclusion En la posmenopausia, el deficit de estrogenos y la resistencia a la insulina se asocian a un incremento de la concentracion de OCN.

Research on mechanisms of chloride ion transport in cement-based materials is relevant to improve the durability of reinforced concrete structures. Conventional chloride-transport models consider a linear diffusion equation, only valid for fully saturated and non-reactive concrete. This work proposes a model of chloride and other ions penetration in saturated concrete considering diffusion, chloride binding, chemical activity and migration. The model uses intrinsic diffusion coefficients. The influence of the ionic pore solution on chloride penetration into concrete is also studied. Chemical activity is introduced by coupling the transport equations to the Pitzer model. The migration is accounted for by imposing the electro-neutrality condition of the pore solution. It is shown that fitting the well known error function to experimentally obtained chloride profiles present results which are difficult to interpret. Moreover, it is shown that, by accounting for solely diffusion and chloride binding, good results are obtained. Contemplating chemical activity and migration slightly improves such results and allows concentration profiles of the present ionic species in the pore solution to be determined. Such profiles are involved in the degradation processes of cement-based materials exposed to aggressive environments.

The stress and immune-related effects of short-term (1, 6 and 24 h) air exposure stress (1 min), bath vaccination with Vibrio anguillarum bacterin, and both stressors combined were evaluated in liver and spleen of Sparus aurata, Danio rerio and Onchorhynchus mykiss. Expression profiles of immune (interleukin 1 beta: il1β; tumor necrosis factor alpha: tnfα; interleukin 10: il10; tumor growth factor beta: tgfβ1; immunoglobulin M: igm; lysozyme: lys; complement protein c3: c3) and stress-related genes (glucocorticoid receptor: gr; heat shock protein 70: hsp70; and enolase) were analysed by RT-qPCR. Cortisol level was assessed by radioimmunoassay. The gene expression patterns in liver and spleen were found to be differentially regulated in a time- and organ-dependent manner among species. In seabream, a higher il1β-driven inflammatory response was recorded. In zebrafish, air exposure stress but not bath vaccination alone modulated most of the changes in liver and spleen immune transcripts. Stressed and vaccinated trout showed an intermediate pattern of gene expression, with a lower upregulation of immune-related genes in liver and the absence of changes in the expression of hsp70 and enolase in spleen (as it was observed in seabream but not in zebrafish). Following air exposure, cortisol levels increased in plasma 1 h post-stress (hps) and then decreased at 6 hps in O. mykiss and D. rerio. By contrast, in S.aurata the cortisol level remained higher at 6 hps suggesting a greater degree of responsiveness to this stressor. When fish were exposed to combined air exposure plus bath vaccination cortisol levels were also augmented at 1 and 6 hps in O. mykiss and S.aurata and restored to basal level at 24 hps, whereas in D. rerio the response was higher in response to the combination of both stressors. In addition, V. anguillarum bacterin vaccination triggered cortisol secretion only in D. rerio, suggesting a greater responsiveness of D. rerio hypothalamic-pituitary-interrenal axis. Overall, comparing the tissue transcription responsiveness, liver was found to be more implicated in the response to handling stress compared to spleen. These results also indicate that a species-specific response accounts for the deviations of stress and immune onset in the liver and spleen in these fish species.

Background The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. Methods We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays. Results Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers. Conclusions Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination., We found no correlation between BNT162b2-associated symptom severity and vaccine-induced antibody titers 1 month after vaccination. Adverse effects inversely correlated with age and weight, whereas symptom severity after first vaccination was predictive of that after second vaccination.

We present the first real-time composition of submicron particulate matter (PM1) in Old Delhi using high-resolution aerosol mass spectrometry (HR-AMS). Old Delhi is one of the most polluted locations in the world, and PM1 concentrations reached ∼ 750 µg m−3 during the most polluted period, the post-monsoon period, where PM1 increased by 188 % over the pre-monsoon period. Sulfate contributes the largest inorganic PM1 mass fraction during the pre-monsoon (24 %) and monsoon (24 %) periods, with nitrate contributing most during the post-monsoon period (8 %). The organics dominate the mass fraction (54 %–68 %) throughout the three periods, and, using positive matrix factorisation (PMF) to perform source apportionment analysis of organic mass, two burning-related factors were found to contribute the most (35 %) to the post-monsoon increase. The first PMF factor, semi-volatility biomass burning organic aerosol (SVBBOA), shows a high correlation with Earth observation fire counts in surrounding states, which links its origin to crop residue burning. The second is a solid fuel OA (SFOA) factor with links to local open burning due to its high composition of polyaromatic hydrocarbons (PAHs) and novel AMS-measured marker species for polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Two traffic factors were resolved: one hydrocarbon-like OA (HOA) factor and another nitrogen-rich HOA (NHOA) factor. The N compounds within NHOA were mainly nitrile species which have not previously been identified within AMS measurements. Their PAH composition suggests that NHOA is linked to diesel and HOA to compressed natural gas and petrol. These factors combined make the largest relative contribution to primary PM1 mass during the pre-monsoon and monsoon periods while contributing the second highest in the post-monsoon period. A cooking OA (COA) factor shows strong links to the secondary factor, semi-volatility oxygenated OA (SVOOA). Correlations with co-located volatile organic compound (VOC) measurements and AMS-measured organic nitrogen oxides (OrgNO) suggest SVOOA is formed from aged COA. It is also found that a significant increase in chloride concentrations (522 %) from pre-monsoon to post-monsoon correlates well with SVBBOA and SFOA, suggesting that crop residue burning and open waste burning are responsible. A reduction in traffic emissions would effectively reduce concentrations across most of the year. In order to reduce the post-monsoon peak, sources such as funeral pyres, solid waste burning and crop residue burning should be considered when developing new air quality policy.

β-glucans are prebiotic and/or food additives used by the aquaculture industry to enhance the immune response of fish. Their efficiency may vary according to their origin and structure. In this study, the immunostimulant effects of two β-glucan types extracted from wild-type baker’s yeast (Saccharomyces cerevisiae) and its null-mutant Gas1 were investigated. Gas1 has a beta-1,3-glucanosyltransferase activity necessary for cell wall assembly. Using a positive (commercial product MacroGard®) and a negative control (a diet without glucans), we evaluated the immune responses and disease resistance of rainbow trout juveniles (mean weight, ~44 g) fed control, low (0.2%) and high (0.5%) doses of Macrogard®, Gas1, and Wild type-β-glucan after a short-term (15 days, D15) or mid-term (36 days, D36) feeding periods. We found that β-glucan supplemented diets did not affect growth performance, mortality, splenic index, or leukocyte respiratory burst activity on D15 nor D36. However, each β-glucan triggered different immune effectors, depending of the doses or length of exposure compared to others and/or the negative control. Indeed, high dose of MacroGard® significantly increased lysozyme activities at D15 compared with the control and other diets (pmcsfra, hepcidin) compared with MacroGard® (p

Background SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination. Methods A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant’s cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity. Discussion This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.

La terapia de resincronizacion cardiaca mediante estimulacion hisiana ha demostrado ser efectiva en pacientes con bloqueo de rama izquierda del haz de His e insuficiencia cardiaca. Paciente masculino, con 47 anos de edad, con insuficiencia cardiaca, fraccion de expulsion del 17% y miocardio dilatada idiopatica, electrocardiograma en ritmo sinusal, bloqueo auriculoventricular de 1.er grado, intervalo PR 400 ms, bloqueo completo de rama derecha del haz de His, bloqueo del fasciculo anterior de la rama izquierda del haz de His, duracion del QRS 200 ms. Se decidio realizar estimulacion selectiva del haz de His. La resincronizacion cardiaca biventricular convencional en pacientes con presencia de bloqueo completo de la rama derecha del haz de His no esta indicada debido a la pobre respuesta al tratamiento. La estimulacion hisiana permite reclutar la rama bloqueada y reestablecer la conduccion a traves de ella, de tal forma que, en ausencia de necrosis, se logre sincronia biventricular. En el caso presentado el reclutamiento de la rama derecha mediante estimulacion hisiana se reflejo en el restablecimiento de la sincronia biventricular, medida por rastreo de marcas (speckle tracking) e incremento significativo de la fraccion de expulsion del ventriculo izquierdo del 17 al 36.6%, con un incremento absoluto del 19.6%. Cardiac resynchronization therapy has proven to be an effective therapy in patients with left bundle branch block and heart failure. Male, 47 years old, heart failure with a left ventricle ejection fraction of 17%, idiopathic heart failure. ECG with sinus rhythm, 1st degree AV block, PR 400 ms, complete right bundle branch block, anterior hemi-fascicle of the left bundle of His, and QRS duration 200 ms. We decided to perform a selective His bundle pacing. In patients with right bundle branch block the biventricular cardiac resynchronization is not indicated due to low treatment response. His bundle pacing allows recruiting the blocked branch and restoring conduction throughout it, therefore, in the absence of necrosis the biventricular synchrony is achieved. We presented a case of His bundle pacing with recruitment of the right bundle branch, which reestablish biventricular synchrony measured by speckle tracking, and with a significant increase of the left ventricle ejection fraction from 17 to 36.6%, with an absolute increase of 19.6%.

The hypothalamic suprachiasmatic nucleus (SCN) is the leading circadian pacemaker in mammals, which synchronizes with environmental light through the retinohypothalamic tract (RHT). Although the SCN regulates circadian rhythms before birth, postnatal synaptic changes are needed for the RHT-SCN pathway to achieve total functional development. However, it is unknown whether visual experience affects developmental maturation. Here, we studied the effects of constant darkness (DD) rearing on the physiology (at pre- and postsynaptic levels) of glutamatergic neurotransmission between RHT and SCN during postnatal development in rats. Upon recording spontaneous and evoked excitatory postsynaptic currents (EPSCs) by electrical stimulation of RHT fibers, we found that DD animals at early postnatal ages (P3-19) exhibited different frequencies of spontaneous EPSCs and lower synaptic performance (short-term depression, release sites, and recruitment of RHT fibers) when compared with their normal light/dark (LD) counterparts. At the oldest age evaluated (P30-35), there was a synaptic response strengthening (probability of release, vesicular re-filling rate, and reduced synaptic depression) in DD rats, which functionally equaled (or surmounted) that of LD animals. Control experiments evaluating EPSCs in ventral SCN neurons of LD rats during day and night revealed no significant differences in spontaneous or evoked EPSCs by high-frequency trains in the RHT at any postnatal age. Our results suggest that DD conditions induce a compensatory mechanism in the glutamatergic signaling of the circadian system to increase the chances of synchronization to light at adult ages, and that the synaptic properties of RHT terminals during postnatal development are not critically influenced by environmental light.

One of the main targets for the use of phytogenics in aquafeeds is the mucosal tissues as they constitute a physical and biochemical shield against environmental and pathogenic threats, comprising elements from both the innate and acquired immunity. In the present study, the modulation of the skin transcriptional immune response, the bacterial growth capacity in skin mucus, and the overall health condition of gilthead seabream (Sparus aurata) juveniles fed a dietary supplementation of garlic essential oil, carvacrol, and thymol were assessed. The enrichment analysis of the skin transcriptional profile of fish fed the phytogenic-supplemented diet revealed the regulation of genes associated to cellular components involved in the secretory pathway, suggesting the stimulation, and recruitment of phagocytic cells. Genes recognized by their involvement in non-specific immune response were also identified in the analysis. The promotion of the secretion of non-specific immune molecules into the skin mucus was proposed to be involved in thein vitrodecreased growth capacity of pathogenic bacteria in the mucus of fish fed the phytogenic-supplemented diet. Although the mucus antioxidant capacity was not affected by the phytogenics supplementation, the regulation of genes coding for oxidative stress enzymes suggested the reduction of the skin oxidative stress. Additionally, the decreased levels of cortisol in mucus indicated a reduction in the fish allostatic load due to the properties of the tested additive. Altogether, the dietary garlic, carvacrol, and thymol appear to promote the gilthead seabream skin innate immunity and the mucus protective capacity, decreasing its susceptibility to be colonized by pathogenic bacteria.

Essential oils (EOs) are promising alternatives to chemotherapeutics in animal production due to their immunostimulant, antimicrobial, and antioxidant properties, without associated environmental or hazardous side effects. In the present study, the modulation of the transcriptional immune response (microarray analysis) and microbiota [16S Ribosomal RNA (rRNA) sequencing] in the intestine of the euryhaline fish gilthead seabream (Sparus aurata) fed a dietary supplementation of garlic, carvacrol, and thymol EOs was evaluated. The transcriptomic functional analysis showed the regulation of genes related to processes of proteolysis and inflammatory modulation, immunity, transport and secretion, response to cyclic compounds, symbiosis, and RNA metabolism in fish fed the EOs-supplemented diet. Particularly, the activation of leukocytes, such as acidophilic granulocytes, was suggested to be the primary actors of the innate immune response promoted by the tested functional feed additive in the gut. Fish growth performance and gut microbiota alpha diversity indices were not affected, while dietary EOs promoted alterations in bacterial abundances in terms of phylum, class, and genus. Subtle, but significant alterations in microbiota composition, such as the decrease in Bacteroidia and Clostridia classes, were suggested to participate in the modulation of the intestine transcriptional immune profile observed in fish fed the EOs diet. Moreover, regarding microbiota functionality, increased bacterial sequences associated with glutathione and lipid metabolisms, among others, detected in fish fed the EOs supported the metabolic alterations suggested to potentially affect the observed immune-related transcriptional response. The overall results indicated that the tested dietary EOs may promote intestinal local immunity through the impact of the EOs on the host-microbial co-metabolism and consequent regulation of significant biological processes, evidencing the crosstalk between gut and microbiota in the inflammatory regulation upon administration of immunostimulant feed additives.

The COVID-19 pandemic will likely take years to control globally, and constant epidemic surveillance will be required to limit the spread of SARS-CoV-2, especially considering the emergence of new variants that could hamper the effect of vaccination efforts. We developed a simple and robust – Phone Screen Testing (PoST) – method to detect SARS-CoV-2-positive individuals by RT-PCR testing of smartphone screen swab samples. We show that 81.3–100% of individuals with high-viral-load SARS-CoV-2 nasopharyngeal-positive samples also test positive for PoST, suggesting this method is effective in identifying COVID-19 contagious individuals. Furthermore, we successfully identified polymorphisms associated with SARS-CoV-2 Alpha, Beta, and Gamma variants, in SARS-CoV-2-positive PoST samples. Overall, we report that PoST is a new non-invasive, cost-effective, and easy-to-implement smartphone-based smart alternative for SARS-CoV-2 testing, which could help to contain COVID-19 outbreaks and identification of variants of concern in the years to come.

Objective The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). Methods We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion

Epileptic seizures in Alzheimer’s disease (AD) patients are rare but still approximately 8 times more common than in the general age-matched population. Experimental and clinical studies have suggested the epileptogenic potential of Aβ, which might represent a principal responsible for the epileptic-like discharges and cognitive decline observed in AD. In addition, an increase in cortical excitability has been demonstrated in AD animal models that may be due to an imbalance of excitatory/inhibitory synaptic transmission. Cortical hyperexcitability has also been demonstrated in the human EEG by the presence of a high proportion of fast oscillatory activities. This review tries to show the mechanisms involved in the generation of the epileptic seizures observed in AD and have been widely studied in animal models. Unfortunately, the EEG analysis in AD is not a standard procedure in clinical practice. Nevertheless, seizures and other electroencephalographic abnormalities are commonly found in AD patients. We suggest that EEG studies in these patients could help to an early diagnosis and inform about the evolution of this disease and their possible cognitive deterioration.

espanolAntecedentes: el sindrome de Andersen-Tawil (ATS) es una canalopatia cardiaca que se hereda de forma autosomica dominante, y se caracteriza por una triada de paralisis periodica, arritmias ventriculares, e incluye algunas caracteristicas dismorficas con penetrancia incompleta y expresion variable que resultan en un diagnostico desafiante. Objetivo: El objetivo del estudio fue describir el fenotipo cardiaco y extracardiaco en una cohorte de pacientes con ETA en riesgo de muerte subita cardiaca (MSC) para mejorar su identificacion clinica precoz. Metodos: En un estudio observacional, transversal, con un muestreo de casos desviado, se incluyeron en el estudio cuatro pacientes con ETA en alto riesgo de ECF. Llevaban las variantes patogenicas heterocigotas c.407C> T [p.Ser136Phe], c.652C> T [p.Arg218Trp] (n = 2) y c.431G> C [p.Gly144Ala] en el gen KCNJ2. Los pacientes fueron evaluados por un cardiologo, un genetista clinico y un fisiatra. Resultados: Un paciente tenia el fenotipo facial clasico y los otros tres tenian manifestaciones sutiles. El grupo de pacientes presento un conjunto diverso de datos clinicos tales como: rostro triangular, frente ancha, ensanchamiento de cejas medial, fosas auriculares, orejas de implantacion baja, ptosis palpebral, labios finos, hipoplasia mandibular y diversos tipos de alteraciones dentarias, unicas. pliegue palmar transversal, camptodactilia y sindactilia. La prueba de esfuerzo prolongado mostro una disminucion en la amplitud porcentual de hasta un 44%, clasificando a los pacientes en tipos IV o V segun la escala de Fournier. Conclusiones: Las manifestaciones extracardiacas fueron un hallazgo comun en esta serie de ETA tipo 1 con alto riesgo de MSC. Su reconocimiento podria ayudar al medico en la identificacion temprana de pacientes con ETA, especialmente al cardiologo, ya que comunmente son referidos solo para evaluacion de arritmias ventriculares. EnglishBackground: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incomplete penetrance and variable expression that result in a challenging diagnosis. Objective: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. Methods: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by cardiologist, a clinical geneticist, and a physiatrist. Results: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier’s scale. Conclusions: Extracardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

Las miopatias inflamatorias son un grupo de enfermedades autoinmunes del musculo esqueletico que pueden afectar otros organos y sistemas, como el aparato cardiovascular1, siendo el mas afectado el miocardio, por ateroesclerosis coronaria. Las anormalidades del ritmo como la taquicardia supraventricular son raras y se presentan en el 0.9% de los casos, las mas frecuentes son los trastornos del sistema de conduccion como los bloqueos de rama y anormalidades de la repolarizacion2.

Infection with the Gram-negative, microaerophilic bacterium Helicobacter pylori induces an inflammatory response and oxidative DNA damage in gastric epithelial cells that can lead to gastric cancer (GC). However, the underlying pathogenic mechanism is largely unclear. Here, we report that the suppression of Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase that specifically removes oxidized bases, is one mechanism through which H. pylori infection may fuel the accumulation of DNA damage leading to GC. Using cultured cell lines, gastric biopsy specimens, primary cells, and human enteroid-derived monolayers from healthy human stomach, we show that H. pylori infection greatly reduces NEIL2 expression. The H. pylori infection-induced downregulation of NEIL2 was specific, as Campylobacter jejuni had no such effect. Using gastric organoids isolated from the murine stomach in coculture experiments with live bacteria mimicking the infected stomach lining, we found that H. pylori infection is associated with the production of various inflammatory cytokines. This response was more pronounced in Neil2 knockout (KO) mouse cells than in WT cells, suggesting that NEIL2 suppresses inflammation under physiological conditions. Notably, the H. pylori-infected Neil2-KO murine stomach exhibited more DNA damage than the WT. Furthermore, H. pylori-infected Neil2-KO mice had greater inflammation and more epithelial cell damage. Computational analysis of gene expression profiles of DNA glycosylases in gastric specimens linked the reduced Neil2 level to GC progression. Our results suggest that NEIL2 downregulation is a plausible mechanism by which H. pylori infection impairs DNA damage repair, amplifies the inflammatory response, and initiates GC.

Cancer is a significant medical issue, being one of the main causes of mortality around the world. The therapies for this pathology depend on the stage in which the cancer is found, but it is usually diagnosed at an advanced stage in which the treatment is chemotherapy. Platinum drugs are among the most commonly used in therapy, unfortunately, one of the main obstacles to this treatment is the development of chemoresistance, which is the ability of cancer cells to evade the effects of drugs. Although some molecular mechanisms involved in resistance to platinum drugs are described, elucidation is still required of others. Secretion of inflammatory mediators such as cytokines and chemokines, by tumor microenvironment components or tumor cells, show direct influence on proliferation, metastasis and progression of cancer and are related to chemoresistance and poor prognosis. In this review, the general mechanisms associated with resistance to platinum drugs, inflammation on cancer development and chemoresistance in various types of cancer will be approached with special emphasis on the current history of CC chemokines subfamily-mediated chemoresistance.

In this paper, the influence of additions of nanosilica (nSi) and microsilica (mSi) on the behav­iour of binary and ternary mixtures in chloride environments is studied. The main objective is to obtain high-performance self-compacting concrete (HPSCC) with a high durability which can meet specific demands in such aggressive environments. Ten blends were manufactured using Portland cement (CEM I 52.5 R) and additions of nSi and mSi in binary and ternary mixtures. The results of three tests frequently used to evaluate resistance to chloride penetration– electrical resistivity, migration and chloride diffusion –were studied and compared. Both binary and ternary mixtures presented significant improvements in chloride resistance, generally in proportion to the total content of the addition. In all the ternary mixtures, high resistivity is obtained, which indicates that such mixtures have a notably low chloride penetrability. Furthermore, these mixtures provided extremely low chloride diffusion coefficients even at small addition ratios. En este artículo se estudia la influencia en el comportamiento frente a cloruros de la adición de nanosílice (nSi) y microsílice (mSi) en mezclas binarias y ternarias. El principal objetivo es obtener un hormigón autocompactante de altas prestaciones con una alta durabilidad frente a estos ambientes agresivos con cloruros. Se prepararon diez dosificaciones usando cemento Portland (CEM I 52.5 R) y adiciones de nSi y mSi en mezclas binarias y ternarias. Se estudiaron y analizaron tres ensayos frecuentemente utilizados para evaluar la resistencia a la penetración de cloruros, resistividad eléctrica, migración y difusión de cloruros. Tanto las mezclas binarias como ternarias presentaron mejoras significativas en la resistencia a cloruros, en general proporcional al contenido de adición. En todas las mezclas ternarias se ha obtenido alta resistividad, indicando una penetrabilidad a cloruros notablemente baja. Estas mezclas proporcionaron un coeficiente de difusión de cloruros extremadamente bajo, incluso para bajos contenidos de adición.

In the present study, we evaluated the effects of a medicinal plant leaf extract (MPLE; 10%, ursolic acid, 3% other triterpenic compounds; 2% verbascoside and 0.05). In order to evaluate the cellular immune competence of fish, an ex vivo assay with splenocytes primary cell culture (SPCC) from both dietary groups was conducted. SPCC were incubated with lipopolysaccharide (LPS) for 24 h and the expression of genes associated to several immune processes was evaluated (humoral immune response, pro- and anti-inflammatory cytokines, cell surface markers, and antioxidant enzymes). Particularly at 4 h post-exposure, dietary supplementation with 0.1% MPLE enhanced SPCC immune response to LPS by the up-regulation of genes involved in humoral immunity (lys, IgM), pro- (tnf-α, il-1β) and anti-inflammatory (tgf-β1, il10) cytokines, the leucocyte cell surface marker cd4, and antioxidative stress enzymes (mn-sod, cat). Therefore, a medicinal plant leaf extract (MPLE) obtained from L. citriodora and S. officinalis may be considered as efficient additive to be used in aquafeed since it does not induce a significant immune reaction under basal conditions, but it provides immune protection after LPS treatment, together with increasing overall fish growth and improvement of feed efficiency values. info:eu-repo/semantics/acceptedVersion

The objective of this study was to analyze the mRNA transcription levels of ten functional genes of P-glycoproteins (P-gp) in free life stages, eggs and infective larvae (L3) and in endoparasitic stages, fourth larval stage (L4) and adult males of two native isolates of Haemonchus contortus: resistant and susceptible to IVM. The IVM resistant isolate was obtained from sheep naturally infected with H. contortus, and the susceptible isolate (with no pressure to IVM) conserved since 1990. The lethal effect of IVM was evaluated under in vitro conditions, which showed significant differences between susceptible and resistant H. contortus L3 isolates (P < 0.01). The IVM susceptible isolate revealed a lethal effect of 79.22% at 11.42 mM, whereas that resistant isolate showed no lethal effect at any of the four assessed concentrations (1.43, 2.85, 5.71 and 11.42 mM) of IVM. The expression levels of ten Hco-pgp genes (1, 2, 3, 4, 9, 10, 11, 12, 14, and 16) were evaluated in the resistant isolate of H. contortus and compared to the susceptible isolate (as control), using two constitutive genes (GAPDH and β-tubulin). Up-regulation at two statistical significant values (P ≤ 0.05, 0.1) was the criterion to associate IVM resistance with the free life and endoparasitic stages of H. contortus. The expression levels in H. contortus adult nematodes showed 5.64 to 127.56-fold increase for Hco-pgp genes 1, 9, 12, 14, and 16, followed by an increase for Hco-pgp-2 (49.75-fold) and Hco-pgp-10 (106.40-fold) in L4, and for Hco-pgp-16 (2.90-fold) in eggs (P ≤ 0.05). In addition, high expression levels with P < 0.1 were detected in H. contortus L3, L4, and adults for Hco-pgp genes 1, 4, 11, 12, and 16, with changes ranging from 2.17 to 29.72-fold. In conclusion, the highest expression was observed in the adult stage of H. contortus, and the most frequent gene with a significant P-value was Hco-pgp-16, revealing it plays an important role in IVM resistance.

The addition of a range of micro- and nano-particles to high-performance concrete has been the focus of recent research. At present, studies are mainly aimed at designing customised mortars, providing them with specific properties for each application. Improving the durability of mortars is one of the main objectives in such research, as a result of increasing environmental concern. The research presented herein analyses the synergistic effect of nanosilica and metakaolin as additives on the service life of cement-based mortars subject to aggressive environments (i.e., chloride exposure) at early ages. The effects of the additives on the durability properties of submerged samples after two and three days of curing were analysed. Tests were conducted on several different properties: resistivity, porosity, mechanical properties, chloride diffusion, and service life. It is observed that metakaolin and nanosilica exhibit a synergistic effect as additives, which is related to porosity refinement and chloride ion binding capacity, which contributes to enhanced resistance against chloride penetration from very early ages.