Protective role of st. John’s wort and its components hyperforin and hypericin against diabetes through inhibition of inflammatory signaling: Evidence from in vitro and in vivo studies

Diabetes mellitus is a very common chronic disease with progressively increasing prevalence. Besides the well-known autoimmune and inflammatory pathogenesis of type 1 diabetes, in many people, metabolic changes and inappropriate lifestyle favor a subtle chronic inflammatory state that contributes to development of insulin resistance and progressive loss of β-cell function and mass, eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of the extract of Hypericum perforatum L. (St. John’s wort, SJW) and its main active ingredients firstly in representative pathological situations on inflammatory basis and then in pancreatic β cells and in obese or diabetic animal models. The simultaneous and long-lasting inhibition of signal transducer and activator of transcription (STAT)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory cytokine-induced β-cell dysfunction/death and insulin resistance make SJW particularly suitable for both preventive and therapeutic use in metabolic diseases. Hindrance of inflammatory cytokine signaling is likely dependent on the hyperforin content of SJW extract, but recent data reveal that hypericin can also exert relevant protective effects, mediated by activation of the cyclic adenosine monophosphate (cAMP)/protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet-induced metabolic abnormalities. Actually, the mechanisms of action of the two main components of SJW appear complementary, strengthening the efficacy of the plant extract. Careful quantitative analysis of SJW components and suitable dosage, with monitoring of possible drug–drug interaction in a context of remarkable tolerability, are easily achievable pre-requisites for forthcoming clinical applications

Time-dependent quantum many-body theory of identical bosons in a double well: Early time ballistic interferences of fragmented and number entangled states

A time-dependent multiconfigurational self-consistent field theory is presented to describe the many-body dynamics of a gas of identical bosonic atoms confined to an external trapping potential at zero temperature from first principles. A set of generalized evolution equations are developed, through the time-dependent variational principle, which account for the complete and self-consistent coupling between the expansion coefficients of each configuration and the underlying one-body wave functions within a restricted two state Fock space basis that includes the full effects of the condensate's mean field as well as atomic correlation. The resulting dynamical equations are a classical Hamiltonian system and, by construction, form a well-defined initial value problem. They are implemented in an efficient numerical algorithm. An example is presented, highlighting the generality of the theory, in which the ballistic expansion of a fragmented condensate ground state is compared to that of a macroscopic quantum superposition state, taken here to be a highly entangled number state, upon releasing the external trapping potential. Strikingly different many-body matter-wave dynamics emerge in each case, accentuating the role of both atomic correlation and mean-field effects in the two condensate states.Comment: 16 pages, 5 figure

Tackling Prejudice and Discrimination Towards Families with Same-Sex Parents: An Exploratory Study in Italy

Though studies have shown that the sexual orientation of parents does not influence their parenting skills or the well-being of their children, prejudice against same-sex families is still very widespread. Research has not sufficiently explored the ways in which parents tackle this prejudice. Using qualitative methodologies, in particular textual analyses, this study has analysed the discourse used by same-sex families to handle the prejudices that they face. The results highlighted that conflicts, which may even be ideological in nature, are sometimes created between traditional families and “atypical” families. These often result in estrangement and isolation from their own family and the communities to which they belong, in turn damaging the growth of the children involved. Furthermore, means for moving beyond conflict, sharing experiences and effectively tackling prejudices are also discussed

Change Detection Techniques with Synthetic Aperture Radar Images: Experiments with Random Forests and Sentinel-1 Observations

This work aims to clarify the potential of incoherent and coherent change detection (CD) approaches for detecting and monitoring ground surface changes using sequences of synthetic aperture radar (SAR) images. Nowadays, the growing availability of remotely sensed data collected by the twin Sentinel-1A/B sensors of the European (EU) Copernicus constellation allows fast mapping of damage after a disastrous event using radar data. In this research, we address the role of SAR (amplitude) backscattered signal variations for CD analyses when a natural (e.g., a fire, a flash flood, etc.) or a human-induced (disastrous) event occurs. Then, we consider the additional pieces of information that can be recovered by comparing interferometric coherence maps related to couples of SAR images collected between a principal disastrous event date. This work is mainly concerned with investigating the capability of different coherent/incoherent change detection indices (CDIs) and their mutual interactions for the rapid mapping of "changed" areas. In this context, artificial intelligence (AI) algorithms have been demonstrated to be beneficial for handling the different information coming from coherent/incoherent CDIs in a unique corpus. Specifically, we used CDIs that synthetically describe ground surface changes associated with a disaster event (i.e., the pre-, cross-, and post-disaster phases), based on the generation of sigma nought and InSAR coherence maps. Then, we trained a random forest (RF) to produce CD maps and study the impact on the final binary decision (changed/unchanged) of the different layers representing the available synthetic CDIs. The proposed strategy was effective for quickly assessing damage using SAR data and can be applied in several contexts. Experiments were conducted to monitor wildfire's effects in the 2021 summer season in Italy, considering two case studies in Sardinia and Sicily. Another experiment was also carried out on the coastal city of Houston, Texas, the US, which was affected by a large flood in 2017; thus, demonstrating the validity of the proposed integrated method for fast mapping of flooded zones using SAR data

Extension of the Discrete-Ordinates Transport Solver IDT to Regular Two-Dimensional Triangular Meshes

In this work, the Integro-Differential Transport solver (IDT), which is one of the transport solvers available in the APOLLO3(R) lattice code, has been extended to handle 2D unstructured meshes. In particular, the previously implemented method of short characteristics (MoSC) used to solve for the spatial variable in the framework of an SN approach has been extended to triangular cells which represent the natural discretization for calculating the hexagonal lattices present in fast reactors. The coefficients of the collision-probability matrices have been evaluated by means of a split-cell algorithm, specialized for dealing with different orientations of the triangle with respect to each discrete ordinate of the SN sweeping. A new sweeping routine for unstructured meshes has been added to IDT. The correct implementation of the method and its robustness with respect to the skewness and the optical thickness of the triangle has been verified. The method of manufactured solutions has been employed to obtain a numerical estimate of the spatial convergence order of the method. The same version of the MoSC has then been implemented in MINARET, another solver available in APOLLO3(R). Finally, the modified IDT applied to an unstructured mesh for the C5G7 benchmark has been successfully benchmarked against MC calculations, and the modified MINARET has been applied to a neutron transport calculation for the RJH research reactor

Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study

<p>Abstract</p> <p>Background</p> <p>In the last decade the importance of ethnicity, socio-economic and gender differences in relation to disease incidence, diagnosis, and prognosis has been realized. Differences in these areas have become a major health policy focus in the United States. Our study was undertaken to examine the demographic and clinical features of chronic myelogenous leukemia (CML) patients presenting initially at the LAC+USC Medical Center, which serves an ethnically diverse population.</p> <p>Results</p> <p>Patients were evenly split by gender, overwhelmingly Hispanic (60.9%), and quite young (median age 39, range 17–65) compared with previously reported CML patient populations. Previous CML studies identified significant anemia (Hgb <12 g/dl), significant thrombocytosis (platelets >450 × 10⁹/l), and significant leukocytosis (WBC >50 × 10⁹/l) as significant adverse pretreatment prognostic factors. Using these indicators, in addition to the validated Hasford and Sokal scores, patients were stratified and analyzed via gender and ethnicity. A significantly greater proportion of women presented with significant anemia (p = 0.019, Fisher's exact test) and significant thrombocytosis (p = 0.041, Fisher's exact test) compared to men, although no differences were found in risk stratification or treatment response. MCV values for women were significantly (p = 0.02, 2-sample t-test) lower than those for men, suggesting iron deficiency anemia. Focusing on ethnicity, Hispanics as a whole had significantly lower Hasford risk stratification (p = 0.046, Fisher's exact test), and significantly greater likelihood (p = 0.016, Fisher's exact test) of achieving 3-month complete haematological remission (CHR) compared with non-Hispanics at LAC+USC Medical Center, though differences in treatment outcome were no longer significant with analysis limited to patients treated with first-line imatinib.</p> <p>Conclusion</p> <p>Female CML patients at LAC+USC Medical Center present with more significant adverse pre-treatment prognostic factors compared to men, but achieve comparable outcomes. Hispanic patients present with lower risk profile CML and achieve better treatment responses compared to non-Hispanic patients as a whole; these ethnic differences are no longer significant when statistical analysis is limited to patients given imatinib as first-line therapy. Our patients achieve response rates inferior to those of large-scale national studies. This constellation of findings has not been reported in previous studies, and is likely reflective of a unique patient population.</p