The Effect of Medical Status on Long-Term Survival of Dental Implants.

Successful dental implant therapy relies on a bone-implant interface that is mechanically strong and capable of dynamic remodeling in response to functional loads. There are a number of medical conditions or therapies that can affect either bone metabolism or the resistance of bone to infection. However, their effects are often mitigated by local factors or individual responses so the impact of these conditions is not clear-cut.

Reformulation of snacks offered to children and adolescents at school kiosks: is this strategy enough or just the tip of the iceberg?

Several studies have reported high overweight and obesity incidence among schoolchildren and adolescents, who mostly consume packaged snacks with critical nutrients exceeding the criteria of international profiling systems during school breaks. Then, the objectives of this work were to reformulate a snack consumed by Argentinian schoolchildren and adolescents (aged 6-13 years) to decrease its critical nutrient contents and to determine if this product would still be accepted. Chocolate chip vanilla cookies were selected for reformulation considering each recommended cut-off point for critical nutrients, since a prohibition of products with warning octagons being offered at schools would come into effect in Argentina.

Skeletal and Mechanistic Diversity in Ir-Catalyzed Cycloisomerizations of Allene-Tethered Pyrroles and Indoles.

Pyrroles and indoles bearing N-allenyl tethers participate in a variety of iridium-catalyzed cycloisomerization processes initiated by a C-H activation step, to deliver a diversity of synthetically relevant azaheterocyclic products. By appropriate selection of the ancillary ligand and the substitution pattern of the allene, the reactions can diverge from simple intramolecular hydrocarbonations to tandem processes involving intriguing mechanistic issues. Accordingly, a wide range of heterocyclic structures ranging from dihydro-indolizines and pyridoindoles to tetrahydroindolizines, as well as cyclopropane-fused tetrahydroindolizines can be obtained.

Gold(III) Auracycles Featuring C(sp)-Au-C(sp) Bonds: Synthesis and Mechanistic Insights into the Cycloauration Step.

The direct auration of arenes is a key step in numerous gold-catalyzed reactions. Although reported more than 100 years ago, understanding of its underlying mechanism has been hampered by the difficulties in the isolation of relevant intermediates given the propensity of gold(III) species to undergo reductive elimination. Here, we report the synthesis and isolation of a new family of intriguing zwitterionic [C(sp)^C(sp)]-auracyclopentanes, as well as of their alkyl-gold(III) precursors and demonstrate their value as mechanistic probes to study the C(sp)-Au bond-forming event.

Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapy.

Antibody-drug conjugates (ADC) represent one of the most successful therapeutic approaches introduced into clinical practice in the last few years. Loncastuximab tesirine (ADCT-402) is a CD19-targeting ADC in which the antibody is conjugated through a protease cleavable dipeptide linker to a pyrrolobenzodiazepine dimer warhead (SG3199). Based on the results of a phase II study, loncastuximab tesirine was recently approved for adult patients with relapsed/refractory large B-cell lymphoma.

High prevalence of microplastics in the digestive tract of Scyliorhinus canicula (Linneaus, 1758) shows the species biomonitoring potential.

Plastic pollution is widespread in oceans and the ingestion of plastic by marine organisms is causing concern about potential adverse effects. The purpose of this study was to analyze the different types of plastics in the digestive tract of female small-spotted catshark (Scyliorhinus canicula). An alkaline digestion method using 10 % potassium hydroxide (KOH), was used.

Characterization and Outcomes of Spanish Patients With Relapsed/Refractory Multiple Myeloma Included in the LocoMMotion Study.

Background: Despite advances in treatments for multiple myeloma (MM), most patients relapse and become refractory to standard drug classes including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 antibodies. The LocoMMotion study showed poor clinical outcomes in triple-class exposed patients with relapsed/refractory MM (RRMM) treated with real-world clinical practice (RWCP) therapy. Here, we report efficacy outcomes for Spanish patients receiving RWCP treatments in the LocoMMotion study compared with the full cohort.

ERBB4-Mediated Signaling Is a Mediator of Resistance to PI3K and BTK Inhibitors in B-cell Lymphoid Neoplasms.

BTK and PI3K inhibitors are among the drugs approved for the treatment of patients with lymphoid neoplasms. Although active, their ability to lead to long-lasting complete remission is rather limited, especially in the lymphoma setting. This indicates that tumor cells often develop resistance to the drugs.

PI3Kδ activation, IL6 over-expression, and CD37 loss cause resistance to the targeting of CD37-positive lymphomas with the antibody-drug conjugate naratuximab emtansine.

Purpose: The transmembrane protein CD37 is expressed almost exclusively in lymphoid tissues, with the highest abundance in mature B cells. CD37-directed antibody- and, more recently, cellular-based approaches have shown preclinical and promising early clinical activity. Naratuximab emtansine (Debio 1562, IMGN529) is an antibodydrug conjugate (ADC) that incorporates an anti-CD37 monoclonal antibody conjugated to the maytansinoid DM1 as payload.

The ATR inhibitor elimusertib exhibits anti-lymphoma activity and synergizes with the PI3K inhibitor copanlisib.

The DNA damage response (DDR) is the cellular process of preserving an intact genome and is often deregulated in lymphoma cells. The ataxia telangiectasia and Rad3-related (ATR) kinase is a crucial factor of DDR in the response to DNA single-strand breaks. ATR inhibitors are agents that have shown considerable clinical potential in this context.

Experimental sickness reduces hypocretin receptor 1 expression in the lateral hypothalamus and ventral tegmental area of female mice.

Recent studies have focused on how sickness behaviours, including lethargy, are coordinated in the brain in response to peripheral infections. Decreased hypocretin (orexin) signalling is associated with lethargy and previous research suggests that hypocretin signalling is downregulated during sickness. However, there are studies that find increases or no change in hypocretin signalling during sickness.

ERBB4-mediated signaling is a mediator of resistance to BTK and PI3K inhibitors in B cell lymphoid neoplasms.

Unlabelled: BTK and PI3K inhibitors are among the drugs approved for the treatment of patients with lymphoid neoplasms. Although active, their ability to lead as single agents to long-lasting complete remission is rather limited especially in the lymphoma setting. This indicates that tumor cells often develop resistance to the drugs.

Targeting IRAK4 with Emavusertib in Lymphoma Models with Secondary Resistance to PI3K and BTK Inhibitors.

Inhibitors of phosphatidylinositol 3-kinase (PI3K) and Bruton tyrosine kinase (BTK) represent a recognized option for the treatment of patients affected by indolent B cell lymphomas. However, small molecules as single agents show limited success in their ability in inducing complete responses, with only partial remission achieved in most patients, suggesting the need for combination therapies. IRAK4 is a protein kinase downstream of the Toll-like receptor signaling (TLR), a driver pathway of secondary tumor° resistance in both hematological and solid tumor malignancies.

Subcapsular Sinus Macrophages Promote Melanoma Metastasis to the Sentinel Lymph Nodes via an IL1α-STAT3 Axis.

During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLN.

Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma.

Inhibitors of the Bromo- and Extra-Terminal domain (BET) family proteins have strong preclinical antitumor activity in multiple tumor models, including lymphomas. Limited single-agent activity has been reported in the clinical setting. Here, we have performed a pharmacological screening to identify compounds that can increase the antitumor activity of BET inhibitors in lymphomas.

Climate risk assessment needs urgent improvement.

Existing constraints in current climate risk assessments make them inappropriate to effectively assess the true exposure of society and businesses to climate-related risk. Using the key constraints to guide a conceptual framework, we identify four cross-cutting and inter-related critical paths for improvement.

Functional Testing to Characterize and Stratify PI3K Inhibitor Responses in Chronic Lymphocytic Leukemia.

Purpose: PI3K inhibitors (PI3Ki) are approved for relapsed chronic lymphocytic leukemia (CLL). Although patients may show an initial response to these therapies, development of treatment intolerance or resistance remain clinical challenges. To overcome these, prediction of individual treatment responses based on actionable biomarkers is needed.

Resistance to PI3Kδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis.

PI3Kδ inhibitors are active in patients with lymphoid neoplasms and a first series of them have been approved for the treatment of multiple types of B-cell lymphoid tumors, including marginal zone lymphoma (MZL). The identification of the mechanisms underlying either primary or secondary resistance is fundamental to optimize the use of novel drugs. Here we present a model of secondary resistance to PI3Kδ inhibitors obtained by prolonged exposure of a splenic MZL cell line to idelalisib.

Transient Focal Neurological Events in Cerebral Amyloid Angiopathy and the Long-term Risk of Intracerebral Hemorrhage and Death: A Systematic Review and Meta-analysis.

Importance: Transient focal neurological episodes (TFNEs) are a frequently overlooked presentation of cerebral amyloid angiopathy (CAA), a condition with prognostic implications that are still not well described.

Objective: To perform a systematic review and meta-analysis to examine the factors associated with incident lobar intracerebral hemorrhage (ICH) and death in patients with CAA presenting with TFNEs.

Data Sources: A systematic review and individual participant meta-analysis including (1) a hospital-based cohort and (2) the results obtained from a systematic search performed in MEDLINE and Embase completed in December 2019.