Activity

Despite the countless efforts made in the last decades, malaria and neglected tropical diseases remain a high-impact health problem in developing countries. Malaria is one of the most severe parasitic diseases, with over 200 million cases and 400 000 deaths in 2019. Parasitic diseases caused by trypanosomatidae, namely Human African Trypanosomiasis, Chagas disease, and leishmaniasis, register the highest rates of mortality amongst all the neglected tropical diseases. In this scenario, chemotherapy remains the first strategy which aims to control and eliminate these diseases. However, the use of outdated, unsafe, and poorly effective drugs, together with the onset of resistance, prompted the researchers to the identification of new and valid targets. The innovative idea, aimed at the development of multi-target ligands addressing two different targets playing key roles in the parasite survival, could represent a valuable strategy. Thanks to this approach, the well-known limitations characterizing the antiparasitic drugs, such as toxicity, rapid resistance onset and narrow spectrum of action, could be overcome. In this review, we now describe the most recent multi-target ligands endowed with antiparasitic effect reported in the literature, focusing our attention on their binding with the targets, inhibitory activities, and potential therapeutic applications.This review intends to summarize the structures of an extensive number of symmetrical-dimeric drugs, having two monomers linked via a bridging entity while emphasizing the large versatility of biologically active substances reported to possess dimeric structures. The largest number of classes of these compounds consist of anticancer agents, antibiotics/antimicrobials, and anti-AIDS drugs. Other symmetrical-dimeric drugs include antidiabetics, antidepressants, analgesics, anti-inflammatories, drugs for the treatment of Alzheimer’s disease, anticholesterolemics, estrogenics, antioxidants, enzyme inhibitors, anti-Parkisonians, laxatives, antiallergy compounds, cannabinoids, etc. Most of the articles reviewed do not compare the activity/potency of the dimers to that of their corresponding monomers. G Protein agonist Only in limited cases, various suggestions have been made to justify unexpected higher activity of the dimers vs. the corresponding monomers. These suggestions include statistical effects, the presence of dimeric receptors, binding of a dimer to two receptors simultaneously, and others. It is virtually impossible to predict which dimers will be preferable to their respective monomers, or which linking bridges will lead to the most active compounds. It is expected that the extensive number of articles summarized, and the large variety of substances mentioned, which display various biological activities, should be of interest to many academic and industrial medicinal chemists.Chronic obstructive pulmonary disease (COPD) is an increasing cause of global morbidity and mortality, with poor long-term outcomes and chronic disability. COPD is a condition with a wide spectrum of clinical presentations, with different phenotypes being identified even among patients with comparable degrees of airflow limitation. Considering the burden of COPD in terms of social and economic costs, in recent years a growing attention has been given to the need of more personalized approaches and patient-tailored rehabilitation programs. In this regard, the systematic analysis of metabolites in biological matrices, namely metabolomics, may become an essential tool in phenotyping diseases. Through the identification and quantification of the small molecules produced during biological processes, metabolomic profiling of biological samples has thus been proposed as an opportunity to identify novel biomarkers of disease outcome and treatment response. Exhaled breath condensate (EBC) and plasma/serum are fluid pools, which can be easily extracted and analyzed. In this review, we discuss the potential clinical applications of the metabolomic profiling of EBC and plasma/serum in COPD.Ferroptosis, which is an iron-dependent, non-apoptotic cell death mechanism, has recently been proposed as a novel approach in cancer treatment. Bearing distinctive features and its exclusive mechanism have put forward the potential therapeutic benefit of triggering this newly discovered form of cell death. Numerous studies have indicated that apoptotic pathways are often deactivated in resistant cells, leading to a failure in therapy. Hence, alternative strategies to promote cell death are required. Mounting evidence suggests that drug-resistant cancer cells are particularly sensitive to ferroptosis. Given that cancer cells consume a higher amount of iron than healthy ones, ferroptosis not only stands as an excellent alternative to trigger cell death and reverse drug-resistance, but also provides selectivity in therapy. This review focuses specifically on overcoming drug-resistance in cancer through activating ferroptotic pathways and brings together the relevant chemotherapeutics-based and nanotherapeutics-based studies to offer a perspective for researchers regarding the potential use of this mechanism in developing novel therapeutic strategies.

Examination of psychometric properties and diagnostic accuracy of the Depression Self-Rating Scale for Adolescents (DSRS-A) as well as development and evaluations of a shorter version, DSRS-A-Screener.

Analyses of component structure and internal consistency were performed in a community-based sample of adolescents

 = 4,506 and among consecutive outpatients from three child psychiatric settings in Sweden (

 = 137). Concurrent validity was measured as a correlation between a summation index of the scale items and the total major depressive disorder (MDD) symptom severity score from the Kiddie Schedule of Affective Disorders and Schizophrenia (K-SADS). Diagnostic accuracy was examined in the clinical sample, with the K-SADS interview as the reference test, by receiver operating characteristic analysis (ROC), calculations of sensitivity, specificity among other measures. With the purpose to select items for a shorter scale, associations between scale items and MDD were examined with binary logistic regression. This shorter scale was thereafter examined similarly.

Based on association with MDD, five items were selected for the brief DSRS-A Screener that showed one component structure, internal consistency Cronbach’s alpha .80 and.82, respectively. In the clinical population concurrent validity was Spearman’s rho .63 and ROC analysis showed AUC .84 (95% CI .78-.91;

 < .001). The optimal cut-off for screening was 2 with sensitivity .85 and specificity of .64.

The DSRS-A Screener compared to the original scale, maintained or improved reliability, validity, and showed moderate diagnostic accuracy.

The DSRS-A Screener compared to the original scale, maintained or improved reliability, validity, and showed moderate diagnostic accuracy.

Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. HRCT resolution is limited while surgical lung biopsy (SLB) carries risks of morbidity/mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis.

We performed a prospective diagnostic accuracy study of EB-OCT in ILD patients with a low-confidence diagnosis undergoing SLB. Primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern.

EB-OCT was performed immediately prior to SLB. The resulting EBlement to HRCT and alternative to SLB.As one of the most severe kinds of neurological damage, spinal cord injury (SCI) contributes to persistent motor dysfunction and involves a large repertoire of gene alterations. The participation of circular RNAs (circRNAs) in neurological recovery following SCI needs to be clarified. In the current work, we attempted to assess the function of hsa_circRNA_0003962/circTYW1 and its underlying mechanism in SCI. By accessing the GEO repository, the expression of circTYW1, microRNA-380 (miR-380), and FGF9 in SCI and sham-operated rats was evaluated. PC12 cells after oxygen-glucose deprivation (OGD) treatment were prepared to mimic the SCI model. circTYW1 and FGF9 were poorly expressed, whereas miR-380 was highly expressed in the spinal cord tissues of SCI rats. circTYW1 promoted neurological recovery in SCI rats and inhibited apoptosis in spinal cord tissues. In PC12 cells exposed to OGD, circTYW1 suppressed PC12 cell apoptosis; however, miR-380 overexpression reversed the protective effect of circTYW1 on PC12 cells. Also, circTYW1 promoted FGF9 expression through competitively binding to miR-380, which activated the ERK1/2 signaling. In summary, our results demonstrated that declines in circTYW1 prevented SCI rats from neurological recovery by regulating the miR-380/FGF9/ERK1/2 axis, which might provide new understanding for SCI treatment.

Patients with schizophrenia are at higher risk of cardiovascular (CVS) related mortality. Close attention is being paid to the clinical utility of readily available CVS markers.

A pilot one-year longitudinal study in inpatients with first-episode psychosis (FEP) was carried out to determine markers of inflammation and endothelial dysfunction (monocyte- and neutrophil-to-lymphocyte ratios) and basal blood pressure, pulse, and derived hemodynamic parameters (PP pulse pressure; RPP rate pressure product; and MAP mean arterial pressure).

After one year, PP and RPP increased, as did systolic blood pressure and heart rate. Systolic blood pressure, PP, total white blood cells, and neutrophils correlated with weight gain. After one year, correlations between monocyte-to-lymphocyte ratio and RPP and MAP were observed.

Our study indicates worsening CVS health over the first year of treatment and emphasises the importance of early monitoring of CVS status using easily accessible parameters to prevent CVS-relateddy in first-episode psychosis patients indicates worsening of CVS health based on these parameters during the first year of treatment, the early monitoring of CVS status is highly relevant in clinical practice.With millions of cases and thousands of deaths every year in Asia and Latin America, dengue fever continues to be of global public health significance. This article uses the concept of ‘medical populism’ to analyse the political construction of the 2019 dengue epidemics in Bangladesh, the Philippines, and Honduras. Through this framework, we examine the narratives of these outbreaks by reconstructing how political actors simplified the discourse, spectacularised the crises, offered multiple knowledge claims, and forged divisions between the people and ‘dangerous others’. Taken together, our case studies, obtained through government, journalistic, and scholarly sources, illuminate the role of medical populists (who are almost always politicians) in defining and responding to public health emergencies, underscoring the performative dimension of disease outbreaks. By detracting attention from less spectacular but more substantive policies and programs, these ‘performances’ of health crises perpetuate health inequities, especially in fragile democracies like the aforementioned Global South countries.