Predicting the outcome of heart failure against chronic-ischemic heart disease in elderly population – Machine learning approach based on logistic regression, case to Villa Scassi hospital Genoa, Italy

Totally 167 patients were admitted at cardiology ward in Villa Scassi hospital, Genoa, Italy. We worked with two control groups: heart failure 59 patients (mean age: 71.37 ± 13.27 years) and chronic-ischemic heart disease 108 patients (mean age: 68.85 ± 11.3 years). Nine parameters: Hb, Serum Creatinine, LDL, HDL, Triglycerides, ALT, AST, hs-cTnI, CRP were evaluated onset to hospitalization. We aimed to identify significant independent predictors relative to the outcome of heart failure versus chronic-ischemic heart disease and select combination of biochemical parameters in logistic regression-based model that would provide on average excellent discrimination to the outcome of heart failure versus chronic-ischemic heart disease in elderly population. Applying 20-fold repeated stratified cross-validation, 4:1 train/test ratio split, we have found that probability of heart failure, provides best discrimination of the outcome of heart failure against chronic-ischemic heart disease

Macro Asset Allocation with Social Impact Investments

Using a unique dataset of 50 listed companies that meet the majority of the OECD requirements for social impact investments, we construct a social impact finance stock index and investigate how investing in social impact firms can contribute to portfolio risk-return performance. We build portfolios with three different methodologies (naïve, Markowitz mean-variance optimization, GARCH-copula model), and we study the performance in terms of returns, Sharpe ratio, utility, and forecast premium based on a constant relative risk aversion function for investors with different levels of risk aversion. Consistent with the idea that social impact investment can improve portfolio risk-return performance, the results of our macro asset allocation analysis show the importance of a large fraction of investor portfolios’ stake committed to social impact investments

Time to redefine endometriosis including its pro-fibrotic nature

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches

Suscetibilidade dos estágios imaturos de Trichogramma pretiosum a óleos inseticidas.

O objetivo desse trabalho foi avaliar a suscetibilidade das fases imaturas do parasitoide Trichogramma pretiosum a óleos vegetais e sintéticos utilizados no controle fitossanitário de pragas.Resumo

Diltiazem downregulates IL-12 production by human dendritic cells

It is well known that IL-12 plays a central role in the initiation and control of allogeneic immune response. It promotes the proliferation of lymphocytes and NK cells, cytotoxic activity of NK cells, and CTL. It was recently shown that IL-12 is involved in the regulation of T helper Th1-Th2 responses by exerting stimulatory effects on Th1 and inhibitory effects on Th2. This regulatory role is believed to result from the ability of IL-12 to induce IFN-γ production in activated T cells and NK cells.[1 and 2] Th1 cytokines (IL-2 and IFN-γ) promote both CTL and delayed-type hypersensitivity (DTH) responses, which are considered the principal effector mechanisms of allograft rejection. Diltiazem, a calcium channel blocker used in organ transplantation, is often included in clinical protocols in association with cyclosporin A and corticosteroids.[3] It was used initially because of its antinephrotoxic and antihypertensive effects, so that the undesirable side effects induced by immunosuppressive therapy could be reduced. We previously studied the effect of diltiazem on human mixed lymphocyte reactions (MLR) and on isolated human monocytes, showing the capacity of this drug to affect proinflammatory cytokine production.[4 and 5] Since dendritic cells (DCs) are the most effective antigen-presenting cells (APCs) to prime naive T cells, we were interested in determining the influence of diltiazem on human DCs. Human DCs generated from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) have been characterised as immature DCs. To become fully potent APCs, DCs must undergo maturation induced either by a proinflammatory signal such as lipopolysaccharide (LPS) or by interaction with CD40L expressed on activated T lymphocytes. [6] The ability of mature DCs to act as potent APCs is due to their high expression of MHC and costimulatory molecules and also to their production of cytokines, especially IL-12. Therefore, we determined the effect of diltiazem on cytokine production by human DCs with a particular interest in IL-1β, IL-6, TNF-α, and IL-12 production

Transient sex-related changes in the mice hypothalamo–pituitary–adrenal (HPA) axis during the acute phase of the inflammatory process

The potential role of endogenous sex hormones in regulating hypothalamo–pituitary–adrenal (HPA) axis function was investigated after a single injection of endotoxin in adult (8 week old) BALB/c mice of both sexes. The effect of LPS on plasma ACTH, corticosterone (B), testosterone and oestradiol (E) levels and on anterior pituitary (AP) ACTH and adrenal B contents at different times after treatment was studied. The results indicate that: (a) basal B but not ACTH plasma levels were significantly higher in female than in male mice; (b) LPS significantly increased both ACTH and B plasma levels over the baseline 2 h after injection, both hormone levels being higher in female than in male mice; (c) although plasma ACTH concentrations recovered the basal value at 72 h after LPS in animals of both sexes, plasma B levels returned to the baseline only at 120 h after treatment; (d) E plasma levels significantly increased 2 h after LPS and returned to the baseline at 72 h post-treatment, in both sexes; (e) at 2 h after LPS, testosterone plasma levels significantly decreased in male mice and increased in female mice, recovering the baseline level at 120 and 72 h after LPS, respectively; (f) AP ACTH content was similar in both sexes in basal condition and it was significantly diminished 72 h post-treatment without sex difference; whereas AP ACTH returned to basal content 120 h after LPS in males, it remained significantly decreased in females; (g) basal adrenal B content was higher in female than in male mice, and it significantly increased in both sexes 2 h post-LPS, maintaining this sex difference. Whereas adrenal B returned to basal content 72 h after treatment in male mice, it remained significantly enhanced up to 120 h post-LPS in female animals. The data demonstrate the existence of a clear sexual dimorphism in basal condition and during the acute phase response as well as in the recovery of the HPA axis function shortly after infection

Consistent Truncation to Three Dimensional (Super-)gravity

For a general three dimensional theory of (super-)gravity coupled to arbitrary matter fields with arbitrary set of higher derivative terms in the effective action, we give an algorithm for consistently truncating the theory to a theory of pure (super-)gravity with the gravitational sector containing only Einstein-Hilbert, cosmological constant and Chern-Simons terms. We also outline the procedure for finding the parameters of the truncated theory. As an example we consider dimensional reduction on S^2 of the 5-dimensional minimal supergravity with curvature squared terms and obtain the truncated theory without any curvature squared terms. This truncated theory reproduces correctly the exact central charge of the boundary CFT.Comment: LaTeX file, 22 page

Contribution of mitochondrial activity to doxorubicin-resistance in osteosarcoma cells

: Osteosarcoma is considered the most common bone tumor affecting children and young adults. The standard of care is chemotherapy; however, the onset of drug resistance still jeopardizes osteosarcoma patients, thus making it necessary to conduct a thorough investigation of the possible mechanisms behind this phenomenon. In the last decades, metabolic rewiring of cancer cells has been proposed as a cause of chemotherapy resistance. Our aim was to compare the mitochondrial phenotype of sensitive osteosarcoma cells (HOS and MG-63) versus their clones when continuously exposed to doxorubicin (resistant cells) and identify alterations exploitable for pharmacological approaches to overcome chemotherapy resistance. Compared with sensitive cells, doxorubicin-resistant clones showed sustained viability with less oxygen-dependent metabolisms, and significantly reduced mitochondrial membrane potential, mitochondrial mass, and ROS production. In addition, we found reduced expression of TFAM gene generally associated with mitochondrial biogenesis. Finally, combined treatment of resistant osteosarcoma cells with doxorubicin and quercetin, a known inducer of mitochondrial biogenesis, re-sensitizes the doxorubicin effect in resistant cells. Despite further investigations being needed, these results pave the way for the use of mitochondrial inducers as a promising strategy to re-sensitize doxorubicin cytotoxicity in patients who do not respond to therapy or reduce doxorubicin side effects