Interprofessional Collaboration and Diabetes Management in Primary Care: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes

The global spread of diabetes poses serious threats to public health requiring a patient-centered approach based both on interprofessional collaboration (IPC) given by the cooperation of several different health professionals, and patients’ perspective through the assessment of Patient-Reported Outcomes (PROs). The aim of the present study is to evaluate the impact of interprofessional collaboration interventions, for the management of type 2 diabetes in primary care settings, through PROs. A systematic review and meta-analysis was conducted querying the PubMed, Scopus and Embase databases. Out of the 1961 papers initially retrieved, 19 met the inclusion criteria. Interprofessional collaboration is significantly associated with an increase in both patient’s satisfaction (SMD 0.32 95% CI 0.05–0.59) and in the mental well-being component of the HRQoL (SMD 0.18; 95% CI 0.06–0.30), and there was also promising evidence supporting the association between an interprofessional approach and an increase in self-care and in generic and specific quality-of-life. No statistical differences were found, supporting the positive impact on IPC interventions on the physical component of the HRQoL, depression, emotional distress, and self-efficacy. In conclusion, the effect of IPC impacts positively on the few areas assessed by PROMs. Policymakers should promote the widespread adoption of a collaborative approach as well as to endorse an active engagement of patients across the whole process of care

Light, medium-weight or heavy? The nature of the first supermassive black hole seeds

Observations of hyper-luminous quasars at $z>6$ reveal the rapid growth of supermassive black holes (SMBHs $>10^9 \rm M_{\odot}$) whose origin is still difficult to explain. Their progenitors may have formed as remnants of massive, metal free stars (light seeds), via stellar collisions (medium-weight seeds) and/or massive gas clouds direct collapse (heavy seeds). In this work we investigate for the first time the relative role of these three seed populations in the formation of $z>6$ SMBHs within an Eddington-limited gas accretion scenario. To this aim, we implement in our semi-analytical data-constrained model a statistical description of the spatial fluctuations of Lyman-Werner (LW) photo-dissociating radiation and of metal/dust enrichment. This allows us to set the physical conditions for BH seeds formation, exploring their relative birth rate in a highly biased region of the Universe at $z>6$. We find that the inclusion of medium-weight seeds does not qualitatively change the growth history of the first SMBHs: although less massive seeds ($<10^3 \rm M_\odot$) form at a higher rate, the mass growth of a $\sim 10^9 \rm M_\odot$ SMBH at $z<15$ is driven by efficient gas accretion (at a sub-Eddington rate) onto its heavy progenitors ($10^5 \rm M_\odot$). This conclusion holds independently of the critical level of LW radiation and even when medium-weight seeds are allowed to form in higher metallicity galaxies, via the so-called super-competitive accretion scenario. Our study suggests that the genealogy of $z \sim 6$ SMBHs is characterized by a rich variety of BH progenitors, which represent only a small fraction ($< 10 - 20\%$) of all the BHs that seed galaxies at $z > 15$.Comment: (21 pages, 18 figures, 2 tables. Accepted for publication in MNRAS

HTS navigator: freely accessible cheminformatics software for analyzing high-throughput screening data

Summary: We report on the development of the high-throughput screening (HTS) Navigator software to analyze and visualize the results of HTS of chemical libraries. The HTS Navigator processes output files from different plate readers' formats, computes the overall HTS matrix, automatically detects hits and has different types of baseline navigation and correction features. The software incorporates advanced cheminformatics capabilities such as chemical structure storage and visualization, fast similarity search and chemical neighborhood analysis for retrieved hits. The software is freely available for academic laboratories

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Uses its C-Terminus to Regulate the A2B Adenosine Receptor

CFTR is an apical membrane anion channel that regulates fluid homeostasis in many organs including the airways, colon, pancreas and sweat glands. In cystic fibrosis, CFTR dysfunction causes significant morbidity/mortality. Whilst CFTR’s function as an ion channel has been well described, its ability to regulate other proteins is less understood. We have previously shown that plasma membrane CFTR increases the surface density of the adenosine 2B receptor (A2BR), but not of the β2 adrenergic receptor (β2AR), leading to an enhanced, adenosine-induced cAMP response in the presence of CFTR. In this study, we have found that the C-terminal PDZ-domain of both A2BR and CFTR were crucial for this interaction, and that replacing the C-terminus of A2BR with that of β2AR removed this CFTR-dependency. This observation extended to intact epithelia and disruption of the actin cytoskeleton prevented A2BR-induced but not β2AR-induced airway surface liquid (ASL) secretion. We also found that CFTR expression altered the organization of the actin cytoskeleton and PDZ-binding proteins in both HEK293T cells and in well-differentiated human bronchial epithelia. Furthermore, removal of CFTR’s PDZ binding motif (ΔTRL) prevented actin rearrangement, suggesting that CFTR insertion in the plasma membrane results in local reorganization of actin, PDZ binding proteins and certain GPCRs

Colloidal Aggregation Causes Inhibition of G Protein-Coupled Receptors

Colloidal aggregation is the dominant mechanism for artifactual inhibition of soluble proteins, and controls against it are now widely deployed. Conversely, investigating this mechanism for membrane-bound receptors has proven difficult. Here we investigate the activity of four well-characterized aggregators against three G protein-coupled receptors (GPCRs) recognizing peptide and protein ligands. Each of the aggregators was active at micromolar concentrations against the three GPCRs in cell-based assays. This activity could be attenuated by either centrifugation of the inhibitor stock solution or by addition of Tween-80 detergent. In the absence of agonist, the aggregators acted as inverse agonists, consistent with a direct receptor interaction. Meanwhile, several literature GPCR ligands that resemble aggregators themselves formed colloids, by both physical and enzymological tests. These observations suggest that some GPCRs may be artifactually antagonized by colloidal aggregates, an effect that merits the attention of investigators in this field

"Integrating China in the International Consortium for Personalized Medicine": The Coordination and Support Action to Foster Collaboration in Personalized Medicine Development between Europe and China

"Integrating China in the International Consortium for Personalized Medicine"(IC2PerMed) is a coordination and support action funded within the Horizon 2020 work program. Following the guidance of the International Consortium for Personalized Medicine (ICPerMed), the project's overarching aim is to align the European Union and China's research agendas in the field of personalized medicine (PM) to enable a swift development of PM approaches in the EU with strong leverage upon EU-Chinese collaboration. Living in the CO-VID-19 era, we are witnessing how the challenges imposed by the pandemic all around the globe have been acting as a catalyst for collaborations and knowledge sharing among national health systems worldwide. Given the strong interest on behalf of both Europe and China in the advancement of PM approaches, now more than ever, a cross-border collaboration between the 2 powers can accelerate the effective translation of such innovation to healthcare systems, advance research, and ensure that such change follows the directions toward the path of sustainability. IC2PerMed developments will be led by European and Chinese experts equally assembled into 3 Working Groups: (1) people and organization, (2) innovation and market, and (3) research and clinical studies in PM. This complex and dynamic network of actions thrives on dialog, cooperation, and alignment of research at national and global levels; work in the direction taken by IC2PerMed shall pave the way toward the realization of PM's full potential, prevent it from becoming a burden for healthcare systems, and, rather, prove that it provides an essential and irreplaceable contribution to their effectiveness, efficiency, and sustainability

Loss of Primary Cilia Potentiates BRAF/MAPK Pathway Activation in Rhabdoid Colorectal Carcinoma: A Series of 21 Cases Showing Ciliary Rootlet CoiledCoil (CROCC) Alterations

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target

N -Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT 2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca2+ mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head twitch and that there was a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor