3D Hydro-mechanical Scenario Analysis to Evaluate Changes of the Recent Stress Field as a Result of Geological CO2 Storage

AbstractA numerical scheme coupling TOUGH2 and the hydro-mechanical simulator OpenGeoSys is used to evaluate the deformations and in situ stress changes induced by CO2 injection at a potential storage site located in the Northeast German Basin (NEGB). Scenario analysis shows that under the given assumptions the vertical displacement of the reservoir is negligible and significant changes in the recent stress field are limited to the surrounding of the injection well. The undertaken assessment is generally representative for CO2 storage in the NEGB. However, simulation results suggest that a larger modeling area needs to be considered to avoid boundary effects

17,β-estradiol inhibits hepatitis C virus mainly by interference with the release phase of its life cycle

Rationale & Aim: Estrogen and estrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of HCV life cycle is/are affected by estrogens. Methods: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate IC50 values. To dissect how 17β-estradiol interferes with phases of HCV life cycle, its effects were measured on the HCV pseudo-particle system (viral entry), the sub-genomic replicon N17/JFH1 and the replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step infection model, infectious supernatants, collected from infected cells exposed to hormones, were used to infect naïve cells. Results: Progesterone and testosterone showed no inhibitory effect on HCV; dehydroepiandrosterone was only mildly inhibitory. In contrast, 17β-estradiol inhibited infection by 64-67% (IC50 values 140 to 160 nM). Fulvestrant reverted the inhibition by 17β-estradiol in a dose-dependent manner. 17β-estradiol exerted only a slight inhibition (<20%) on HCV pseudo-particles, and had no effect on cells either transiently or stably (Huh7-J17 cells) expressing the N17/JFH1 replicon. In the dual-step infection model, a significant IC50 decline occurred between primary (134 nM) and secondary (100 nM) infections (p=0.02), with extracellular HCV RNA and infectivity being reduced to a higher degree in comparison to its intracellular counterpart. Conclusions: 17β-estradiol inhibits HCV acting through its intracellular receptors, mainly interfering with late phases (assembly/release) of the HCV life cycle

Engineering Silicon Nanocrystals: Theoretical study of the effect of Codoping with Boron and Phosphorus

We show that the optical and electronic properties of nanocrystalline silicon can be efficiently tuned using impurity doping. In particular, we give evidence, by means of ab-initio calculations, that by properly controlling the doping with either one or two atomic species, a significant modification of both the absorption and the emission of light can be achieved. We have considered impurities, either boron or phosphorous (doping) or both (codoping), located at different substitutional sites of silicon nanocrystals with size ranging from 1.1 nm to 1.8 nm in diameter. We have found that the codoped nanocrystals have the lowest impurity formation energies when the two impurities occupy nearest neighbor sites near the surface. In addition, such systems present band-edge states localized on the impurities giving rise to a red-shift of the absorption thresholds with respect to that of undoped nanocrystals. Our detailed theoretical analysis shows that the creation of an electron-hole pair due to light absorption determines a geometry distortion that in turn results in a Stokes shift between adsorption and emission spectra. In order to give a deeper insight in this effect, in one case we have calculated the absorption and emission spectra going beyond the single-particle approach showing the important role played by many-body effects. The entire set of results we have collected in this work give a strong indication that with the doping it is possible to tune the optical properties of silicon nanocrystals.Comment: 14 pages 19 figure

A marketing approach to innovation in chronic care: new value for patients in Lombardian region

Introduction : Disease management programs typically refer to multidisciplinary efforts to improve the quality and cost-effectiveness of care for patients with chronic diseases. This trend highlights the importance of assessing the clinical and public policy implications of this phenomenon from the perspectives of patients' best interests and quality of care. This approach has been implemented in Lombardia Region (Italy) since 2011 for a set of chronic diseases in a sample of 5 Local Healthcare Units. The project is called CReG (Chronic Related Group) and aims to define a new organizational model to coordinate and integrate primary care for chronic patients out of the traditional "hospital-based" approach, with a key role played by Accura, a private disease management company. Theory and methods : Our research is focused on the evaluation of this project, in order to understand the clinical, social and economic value created for the enrolled patients based on qualitative and quantitative research: 3 focus groups involving chronic patients and their caregivers, family practitioners and nurses and 315 CATI (Computer-Assisted Telephone Interviews) to chronic patients. Results : The analysis shows that the patient's overall feeling towards this approach is positive. Data depict an improvement in trust towards the general practitioner but no evidence of significant change in trust towards Regional Health Service. The quality of human interaction with case managers (during consultations as well as during phone calls) is a critical success factor. Data show that MD's prescriptions to patients enrolled in CReG are more compliant with clinical practice guidelines, just with reference to healthcare services and not to drugs. Discussion : From the performed analysis, it is possible to see how patients' attitude towards CReG changes according to the degree of services usage. Conclusion : The analysis shows that Lombardia Region CReG definitely creates value for chronic patients. Some concern arise as for the economic burden of the prescriptions for patients who perceive an increase of the out-of-pocket financial costs and might reduce their compliance in drug consumption. Lessons learned : In order to maximize the perceived value of a disease management program, four value elements should be emphasized: (1) the quality of human interaction, (2) the availability of mobile tools and apps, (3) the deployment of a full range of opportunities for patient empowerment and (4) the existence of a digital social environment for patients' experience sharing. Limitations : The assessment was conducted in an early stage of CReG and patients' usage of the offered services was still limited. Suggestions for future research : A second assessment should be performed in a mature stage of CReG projects, including a benchmark analysis between different geographical areas

Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis

Iodine status and supplementation in pregnancy: an overview of the evidence provided by meta-analyses

Iodine supplementation during pregnancy in areas with mild-moderate defciency is still a matter of debate. The present study aimed at systematically reviewing currently available evidences provided by meta-analyses with the aim to further clarify controversial aspects regarding the need of iodine supplementation in pregnancy as well as to provide guidance on clinical decision-making, even in areas with mild-moderate defciency. Medline, Embase and Cochrane search from 1969 to 2022 were performed. For the purpose of this review, only studies containing meta-analytic data were selected. A total of 7 meta-analyses were retrieved. Four meta-analyses evaluated the relationship between iodine status during pregnancy and neonatal and maternal outcomes suggesting the existence of a U-shaped correlation between iodine status and several maternal and neonatal consequences, especially if iodine status is evaluated at the beginning of pregnancy. Three meta-analyses evaluating the results of intervention trials failed to provide straightforward conclusions on the benefts of iodine supplementation in pregnant women in areas with mild-moderate iodine defciency. Although evidence coming from meta-analyses suggests a role of iodine status during pregnancy in determining maternal and child outcomes, results of meta-analyses of intervention trials are still controversial. Several factors including, degree of iodine defciency, and pooling studies conducted in areas with diferent iodine intake, may account for the lack of benefts reported by metaanalyses of intervention trials. More high-quality, randomized, controlled trials including information on timing, dose and regimen of iodine supplementation are needed to further elucidate this issue

Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder

Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7, PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance–related processes may be involved in several phenotypes, including the TRD

Timed rise from floor as a predictor of disease progression in Duchenne muscular dystrophy: An observational study

The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS).The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01).Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression