Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) detected in the liver has been considered a severe complication of hematopoietic stem cell transplantation (HSCT). SOS/VOD is ...characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites. The severe forms of the disease may result in multi-organ dysfunction (MOD) with a high mortality rate (>80%). The development of SOS/VOD can be rapid and unpredictable. Therefore, early identification and severity assessment is crucial in facilitating prompt diagnosis and timely treatment. Effective treatment and potential prophylaxis with defibrotide highlight the need for characterizing a sub-group of patients at high risk for SOS/VOD. Moreover, antibodies that are conjugated with calicheamicin, gemtuzumab, and inotuzumab ozogamicin, have led to renewed interest in this syndrome. Evaluation and management of serious adverse events associated with gemtuzumab and inotuzumab ozogamicin are recommended. We review hepatic-, transplant- and patient-related risk factors, criteria for diagnosis and grading classification, and SOS/VOD potential biomarkers. Furthermore, we examine pathogenesis, clinical presentation, diagnostic criteria, risk factors, prophylaxis, and treatment of SOS/VOD occurring post HSCT. Moreover, we aim to provide an up-to-date summary of molecular advances in the diagnosis and management of SOS/VOD. We performed a comprehensive review of the literature and examined the recently available data, mostly using the PubMed and Medline search engines for original articles published over the last decade. In the era of precision medicine, our review provides up-to-date knowledge of genetic or sera markers for SOS/VOD with the goal of identifying a subset of high-risk patients.
We employ graphene saturable absorption for the theoretical demonstration of saturable absorption mirrors based on planar silicon photonic Bragg gratings. Two geometries are investigated, that of a ...silicon wire grating and a silicon slot grating, showcasing the increased light-matter interaction of the high-confinement slot waveguide. The gratings are designed in the linear regime for single mode operation, low footprint and broadband operation in the near infrared optical communications frequency range. The saturable absorption effect is introduced through the saturation of graphene's interband surface conductivity, and we discuss the necessary biasing conditions and applicability of our CW approach on ps-long pulses. We also rigorously include other, possibly detrimental, nonlinear effects, such as silicon's Kerr effect and two photon absorption, and graphene's Kerr effect. These effects are proven to have a negligible impact on the operation of the graphene saturable absorber mirror, thanks to the much lower power threshold of graphene's saturable absorption. Finally, we calculate the nonlinear reflectance and transmittance of the graphene-enhanced Bragg gratings and demonstrate that they can provide high modulation depths at low saturation powers, both highly valued characteristics of saturable absorber mirrors for mode locking applications in view of next-generation integrated pulsed photonic light sources.
Abstract
Background
To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.
...Methods
The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25–39, 40–49, 50–59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.
Results
A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5, 10.0 and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (
p
-value≤0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.
Conclusions
High level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the plethora of good quality publicly available information and the timely management of the pandemic at its early stages in Greece. Information campaigns for the COVID-19 pandemic should be encouraged even after the lifting of lockdown measures to increase public awareness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different ...extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated.
We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year. Simultaneous ultrasensitive subpopulation staining/hybridization in situ(SUSHI) was performed to identify HIVpt in CD4+ T-cells and in the CD4+CD45RO+ T-cell subpopulation. The differential mRNA expression of P-glycoprotein(P-gp/ABCB1) and multidrug resistance-associated protein-1(MRP1/ABCC1) was also evaluated. Univariate logistic regression models were used to evaluate predictors of HIVpt.
In the CD4+ T-cell population, HIVpt affected 13/30 of patients on EFV versus 10/21 on ATV. In the CD4+CD45RO+ T-cell population, HIVpt was present in 14/30 of patients on EFV versus 15/21 on ATV. A trend for association was observed between the risk of HIVpt and ATV treatment in the CD4+CD45RO+ T-cell population (OR 2.86, 95% CI 0.87-9.37, p = 0.083). HIVpt status was not associated with loss of virological suppression or CD4 evolution. We found no evidence of differential expression of the drug efflux transporters P-gp and MRP1.
Further study is required to evaluate whether the HIVpt profile in specific cell populations may differ across different antiretroviral regimens and to elucidate the potential clinical impact.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 ...subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60;
= 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.
Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis ...focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2-1518 subtype A1 sequences and 168 MTCs in the range of 2-218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34,
< 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05,
< 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57,
= 0.019), younger age (OR = 0.96,
< 0.001), and more recent sampling (time period: 2011-2015 vs. 1999-2005, OR = 3.83,
< 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.
An ever-growing amount of accumulated data has materialized in several scientific fields, due to recent technological progress. New challenges emerge in exploiting these data and utilizing the ...valuable available information. Causal models are a powerful tool that can be employed towards this aim, by unveiling the structure of causal relationships between different variables. The causal structure may avail experts to better understand relationships, or even uncover new knowledge. Based on 963 patients with coronary artery disease, the robustness of the causal structure of single nucleotide polymorphisms was assessed, taking into account the value of the Syntax Score, an index that evaluates the complexity of the disease. The causal structure was investigated, both locally and globally, under different levels of intervention, reflected in the number of patients that were randomly excluded from the original datasets corresponding to two categories of the Syntax Score, zero and positive. It is shown that the causal structure of single nucleotide polymorphisms was more robust under milder interventions, whereas in the case of stronger interventions, the impact increased. The local causal structure around the Syntax Score was studied in the case of a positive Syntax Score, and it was found to be resilient, even when the intervention was strong. Consequently, employing causal models in this context may increase the understanding of the biological aspects of coronary artery disease.
We present the concept, analysis and design of a nonreciprocal system of coupled nonlinear waveguides, operating at the near infrared. We exploit the spatial asymmetry induced by the exceptional ...points of a non-Hermitian coupler which, combined with saturable absorption in the nonlinear regime, can break Lorentz reciprocity. In this work, we introduce asymmetric losses in a pair of coupled silicon waveguides by overlaying only one of them with unbiased graphene, subject to saturable absorption. The device can be used as a broadband half-duplex isolator: a two-port component offering unidirectional transmission of high-power signals.
Vitamin E, a naturally occurring antioxidant, has been found to reduce atherosclerotic lesion formation in animal models as well as cardiovascular morbidity in several observational studies. However, ...a number of case-control and prospective cohort studies failed to confirm its value in the primary and secondary prevention of morbidity and mortality from coronary artery disease. Several small or larger randomized interventional trials completed to date failed to resolve the conflict. Notably, even in large, well-conducted prospective epidemiologic studies, the potential effects of residual confounding may be on the same order of magnitude as the reported benefit. The response to vitamin E supplementation in specific patient subpopulations with chronic inflammation and/or higher degrees of oxidative stress has not been studied as yet. Therefore, further large randomized interventional trials are warranted to clarify accurately the role of vitamin E in the primary and secondary prevention of atherosclerotic coronary disease in these patient groups.
PDF
