The impact of health status and human capital formation on regional performance: Empirical evidence

The purpose of this paper is to analyze the impact of health on growth, assuming that it is a fundamental component of the human capital of a region along with education. Various measures of population health status are used, together with a health index generated by Principal Component Analysis. Potential endogeneity between health and growth is controlled for using instrumental variable regressions and dynamic panel data. The results show a positive effect of a change in health status on regional output and a negative effect of proxy variables for health limitations on regional performance. This corroborates the importance of investing in health along with education with the aim of improving not only the well-being of individuals but the human capital and growth of a region

Add-on inhaled budesonide in the treatment of hospitalised patients with COVID-19 : a randomised clinical trial

SARS-CoV-2 vaccines have been extremely effective to reduce the incidence of severe COVID19 [1-3], but effective and safe treatments of the acute infection are still limited [4, 5]. An uncontrolled pulmonary inflammatory response to SARS-CoV-2 is considered a key pathogenic mechanism of COVID19 progression [6], so systemic dexamethasone is recommended in severe cases [5, 7]. On the other hand, in very mild patients at home inhaled corticosteroids (ICS) may prevent disease progression [8-11]. Whether ICS prevent disease progression too in patients hospitalised because of COVID19 has not been explored before. Accordingly, we designed an investigator-initiated, open-label, randomised clinical trial (RCT) to explore the efficacy of adding inhaled budesonide to usual care to prevent disease progression in patients hospitalised because of COVID19 pneumonia. We also monitored carefully the safety of this intervention since there are concerns about the use of systemic corticosteroids in other viral (influenza) lung infections [12]

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer

Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-xL, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic β-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-xL upon exogenous over-expression

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

A first prototype of C6_6 D6_6 total-energy detector with SiPM readout for neutron capture time-of-flight experiments

Low efficiency total-energy detectors (TEDs) are one of the main tools for neutron capture cross section measurements utilizing the time-of-flight (TOF) technique. State-of-the-art TEDs are based on a C$_6$ D$_6$ liquid-scintillation cell optically coupled to a fast photomultiplier tube. The large photomultiplier tube represents yet a significant contribution to the so-called neutron sensitivity background, which is one of the most conspicuous sources of uncertainty in this type of experiments. Here we report on the development of a first prototype of a TED based on a silicon-photomultiplier (SiPM) readout, thus resulting in a lightweight and much more compact detector. Apart from the envisaged improvement in neutron sensitivity, the new system uses low voltage (+28 V) and low current supply ( ∼ 50 mA), which is more practical than the ∼ kV supply required by conventional photomultipliers. One important difficulty hindering the earlier implementation of SiPM readout for this type of detector was the large capacitance for the output signal when all pixels of a SiPM array are summed together. The latter leads to long pulse rise and decay times, which are not suitable for time-of-flight experiments. In this work we demonstrate the feasibility of a Schottky-diode multiplexing readout approach, that allows one to preserve the excellent timing properties of SiPMs, hereby paving the way for their implementation in future neutron TOF experiments

Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy

The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. Surprisingly, preclinical trials with an inhibitory monoclonal antibody to IGF-1R did not significantly impact tumor growth, prompting us to investigate the involvement of IR. The levels of IR were found to be significantly up-regulated during multistep progression from hyperplastic lesions to islet tumors. Its functional involvement was revealed by genetic disruption of the IR gene in the oncogene-expressing pancreatic β cells, which resulted in reduced tumor burden accompanied by increased apoptosis. Notably, the IR knockout tumors now exhibited sensitivity to anti–IGF-1R therapy; similarly, high IR to IGF-1R ratios demonstrably conveyed resistance to IGF-1R inhibition in human breast cancer cells. The results predict that elevated IR signaling before and after treatment will respectively manifest intrinsic and adaptive resistance to anti–IGF-1R therapies