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Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response ...have not been investigated.
To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu.
Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed.
SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells.
S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.
The Pierre Auger Cosmic Ray Observatory Aab, A.; Abreu, P.; Aglietta, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2015, Letnik:
798, Številka:
C
Journal Article
Recenzirano
Odprti dostop
The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world׳s largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and ...characteristics of cosmic rays above 1017eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water Cherenkov particle detector stations spread over 3000km2 overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5km2, 61-detector infilled array with 750m spacing. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000km2sryr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Observatory.
Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-α (TNF-α) is implicated in the ...pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed immunoglobulin G1 (IgG1) murine–human chimeric monoclonal antibody that binds the soluble subunit and the membrane-bound precursor of TNF-α, blocking its interaction with receptors and causing lysis of cells that produce TNF-α. In this study we retrospectively evaluated 134 patients who had steroid-refractory acute GVHD. Of these, 21 who received infliximab as a single agent were analyzed. The overall response rate was 67% (n = 14), and 13 patients (62%) experienced complete response (CR). Five patients (24%) did not respond, and 2 (10%) had progressive GVHD. None had a toxic reaction to infliximab. Ten patients (48%) had 18 fungal infections, including Aspergillus species in 7 and Candida species in 10. Seventeen patients (81%) had bacterial infections, including 32 gram-positive and 8 gram-negative infections. Viral infections, primarily cytomegalovirus reactivation, occurred in 14 patients (67%). The Kaplan-Meier estimate of overall survival was 38%. In conclusion, infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD, particularly with gastrointestinal tract involvement. Survival after steroid-resistant acute GVHD continues to be problematic. The possibility of excessive fungal and other infections must be explored further.
To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6.
To measure the ...severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient.
An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count.
Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.
Sporotrichosis is a subacute or chronic subcutaneous infection, caused by the fungus Sporothrix schenkii complex, occurring in human and animal tissues. Potassium iodide and itraconazole have been ...used as effective therapy for first-choice treatment, while amphotericin B may be indicated for disseminated infection. However, the adverse effects of potassium iodide and amphotericin B or the long duration of therapy with itraconazole often weigh against their use, leading to the search for alternatives for the treatment of severe infections. Terpinen-4-ol and farnesol are components of essential oils present in many plant species and have been described to have antifungal activity against microorganisms. In this study, 40 strains of Sporothrix spp. were tested for the susceptibility to terpinen-4-ol and farnesol. Changes in cytoplasmic membrane permeability were also investigated. Terpenes inhibited all Sporothrix strains with MIC values ranging from 87.9 to 1,429.8 μg/ml for terpinen-4-ol and from 0.003 to 0.222 μg/ml for farnesol. The MFC values ranged from 177.8 to 5,722.6 μg/ml and from 0.027 to 0.88 μg/ml, respectively, for terpinen-4-ol and farnesol. Farnesol was the most active compound for the Sporothrix strains. Significant loss of 260 and 280 nm-absorbing material did not occur after treatment with concentrations equivalent to the MIC and sub-MIC of the tested terpenes, when compared to corresponding untreated samples. The failure of terpenes to lyse Sporothrix cells suggests that their primary mechanism of action is not by causing irreversible cell membrane damage. Thus, new studies are needed to better understand the mechanisms involved in the antifungal activity.
Purpose: The COVID-19 pandemic posed a worldwide challenge, leading to radical changes in healthcare. The primary objective of the study was to assess the impact of the COVID-19 pandemic on birth, ...vaginal delivery, and cesarian section (c-section) rates. The secondary objective was to compare the maternal mortality before and after the pandemic. Patients and Methods: Time-series cohort study including data of all women admitted for childbirth (vaginal delivery or c-section) at the maternities in the Public Health System of Federal District, Brazil, between March 2018 and February 2022, using data extracted from the Hospital Information System of Brazilian Ministry of Health (SIH/DATASUS) on September 30, 2022. Causal impact analysis was used to evaluate the impact of COVID-19 on birth, vaginal delivery, and c-section using the CausalImpact R package, and a propensity score matching was used to evaluate the effect on maternal mortality rate using the Easy R (EZR) software. Results: There were 150,617 births, and considering total births, the effect of the COVID-19 pandemic was not statistically significant (absolute effect per week: 5.5, 95% CI: -24.0-33.4). However, there was an increase in c-sections after COVID-19 (absolute effect per week: 18.1; 95% CI: 11.9-23.9). After propensity score matching, the COVID-19 period was associated with increased maternal mortality (OR: 3.22, 95% CI: 1.53-6.81). The e-value of the adjusted OR for the association between the post-COVID-19 period and maternal mortality was 5.89, with a 95% CI: 2.43, suggesting that unmeasured confounders were unlikely to explain the entirety of the effect. Conclusion: Our study revealed a rise in c-sections and maternal mortality during the COVID-19 pandemic, possibly due to disruptions in maternal care. These findings highlight that implementing effective strategies to protect maternal health in times of crisis and improve outcomes for mothers and newborns is crucial. Keywords: COVID-19, cesarean section, maternal health services, maternal mortality
The COVID-19 pandemic posed a worldwide challenge, leading to radical changes in surgical services. The primary objective of the study was to assess the impact of COVID-19 on elective and emergency ...surgeries in a Brazilian metropolitan area. The secondary objective was to compare the postoperative hospital mortality before and during the pandemic.PurposeThe COVID-19 pandemic posed a worldwide challenge, leading to radical changes in surgical services. The primary objective of the study was to assess the impact of COVID-19 on elective and emergency surgeries in a Brazilian metropolitan area. The secondary objective was to compare the postoperative hospital mortality before and during the pandemic.Time-series cohort study including data of all patients admitted for elective or emergency surgery at the hospitals in the Public Health System of Federal District, Brazil, between March 2018 and February 2022, using data extracted from the Hospital Information System of Brazilian Ministry of Health (SIH/DATASUS) on September 30, 2022. A causal impact analysis was used to evaluate the impact of COVID-19 on elective and emergency surgeries and hospital mortality.Patients and MethodsTime-series cohort study including data of all patients admitted for elective or emergency surgery at the hospitals in the Public Health System of Federal District, Brazil, between March 2018 and February 2022, using data extracted from the Hospital Information System of Brazilian Ministry of Health (SIH/DATASUS) on September 30, 2022. A causal impact analysis was used to evaluate the impact of COVID-19 on elective and emergency surgeries and hospital mortality.There were 174,473 surgeries during the study period. There was a reduction in overall (absolute effect per week: -227.5; 95% CI: -307.0 to -149.0), elective (absolute effect per week: -170.9; 95% CI: -232.8 to -112.0), and emergency (absolute effect per week: -57.7; 95% CI: -87.5 to -27.7) surgeries during the COVID-19 period. Comparing the surgeries performed before and after the COVID-19 onset, there was an increase in emergency surgeries (53.0% vs 68.8%, P < 0.001) and no significant hospital length of stay (P = 0.112). The effect of the COVID-19 pandemic on postoperative hospital mortality was not statistically significant (absolute effect per week: 2.1, 95% CI: -0.01 to 4.2).ResultsThere were 174,473 surgeries during the study period. There was a reduction in overall (absolute effect per week: -227.5; 95% CI: -307.0 to -149.0), elective (absolute effect per week: -170.9; 95% CI: -232.8 to -112.0), and emergency (absolute effect per week: -57.7; 95% CI: -87.5 to -27.7) surgeries during the COVID-19 period. Comparing the surgeries performed before and after the COVID-19 onset, there was an increase in emergency surgeries (53.0% vs 68.8%, P < 0.001) and no significant hospital length of stay (P = 0.112). The effect of the COVID-19 pandemic on postoperative hospital mortality was not statistically significant (absolute effect per week: 2.1, 95% CI: -0.01 to 4.2).Our study showed a reduction in elective and emergency surgeries during the COVID-19 pandemic, possibly due to disruptions in surgical services. These findings highlight that it is crucial to implement effective strategies to prevent the accumulation of surgical waiting lists in times of crisis and improve outcomes for surgical patients.ConclusionOur study showed a reduction in elective and emergency surgeries during the COVID-19 pandemic, possibly due to disruptions in surgical services. These findings highlight that it is crucial to implement effective strategies to prevent the accumulation of surgical waiting lists in times of crisis and improve outcomes for surgical patients.
The purpose of this study was to determine the effects of in vivo GnRH treatment on mRNA expression of IL-1β system in bovine granulosa cells from preovulatory follicles and to analyze the in vitro ...effect of gonadotropins on the IL-1β system gene expression in cumulus cells. Moreover, the additive effect of IL-1β on cumulus expansion, gene expression and ultrastructural integrity of COCs cultured in vitro was evaluated. In vivo studies in granulosa cells demonstrated that IL-1RA mRNA levels were increased after 24h of GnRH treatment. Similarly, the presence of gonadotropins increased the levels of mRNAs for IL-1R1 and IL-1RA in cumulus cells after 24h of culture in vitro. The presence of IL-1β in culture medium did not influence cumulus expansion, but it increased the expression of mRNAs for IL-1β, IL-1RA, HAS2 and iNOS after COC culture. In addition, the ultrastructure of COCs cultured in vitro in the presence of IL-1β was maintained. In conclusion, IL-1RA mRNA is upregulated in granulosa cells at later stages of the ovulatory process in cattle. In cumulus cells, mRNA expression of IL-1RI and IL-1RA is induced by gonadotropins and IL-1β maintains the ultrastructure of COC cultured in vitro.
•IL-1RA mRNA is upregulated in bovine granulosa cells after in vivo GnRH treatment.•mRNA expression of IL-1RI and IL-1RA is induced by gonadotropins in cultured cumulus cells.•IL-1β increases iNOS mRNA in cultured cumulus cells in a time-dependent manner.•IL-1β maintains the ultrastructure of COC cultured in vitro.
Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is ...already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius A. Also the events detected simultaneously by the surface and fluorescence detectors (the ‘hybrid’ data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.
We aimed at investigating the relationship between particulate matter (PM) and daily admissions for cardiovascular diseases (CVDs) at national level in Italy.
Daily numbers of cardiovascular ...hospitalizations were collected for all 8084 municipalities of Italy, in the period 2013-2015. A satellite-based spatiotemporal model was used to estimate daily PM10 (inhalable particles) and PM2.5 (fine particles) concentrations at 1-km2 resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and cardiovascular admissions. Flexible functions were estimated to explore the shape of the associations at low PM concentrations, also in non-urban areas. We analysed 2 154 810 acute hospitalizations for CVDs (25% stroke, 24% ischaemic heart diseases, 22% heart failure, and 5% atrial fibrillation). Relative increases of total cardiovascular admissions, per 10 µg/m3 variation in PM10 and PM2.5 at lag 0-5 (average of last 6 days since admission), were 0.55% (95% confidence intervals: 0.32%, 0.77%) and 0.97% (0.67%, 1.27%), respectively. The corresponding estimates for heart failure were 1.70% (1.28%, 2.13%) and 2.66% (2.09%, 3.23%). We estimated significant effects of PM10 and PM2.5 also on ischaemic heart diseases, myocardial infarction, atrial fibrillation, and ischaemic stroke. Associations were similar between less and more urbanized areas, and persisted even at low concentrations, e.g. below WHO guidelines.
PM was robustly associated with peaks in daily cardiovascular admissions, especially for heart failure, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines for PM10 and PM2.5 are not sufficient to protect public health.
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