Moss establishment success is determined by the interaction between propagule size and species identity.

Colonization of new habitat patches is a key aspect of metacommunity dynamics, particularly for sessile organisms. Mosses can establish in new patches through fragmentation, with different vegetative structures acting as propagules. Despite the importance of these propagules for successful colonization the specific aspects that favour moss colonization by vegetative propagules remain poorly understood, including the effect of propagule size.

Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis.

Objective: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate.

Methods: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients.

Phase I Study of Taminadenant (PBF509/NIR178), an Adenosine 2A Receptor Antagonist, with or without Spartalizumab (PDR001), in Patients with Advanced Non-Small Cell Lung Cancer.

Purpose: The adenosine 2A receptor (A2AR) mediates the immunosuppressive effects of adenosine in the tumor microenvironment and is highly expressed in non-small cell lung cancer (NSCLC). Taminadenant (PBF509/NIR178) is an A2AR antagonist able to reactivate the antitumor immune response.

Patients And Methods: In this phase I/Ib, dose-escalation/expansion study, patients with advanced/metastatic NSCLC and ≥1 prior therapy received taminadenant (80-640 mg, orally, twice a day) with or without spartalizumab (anti-programmed cell death-1, 400 mg, i.

ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges.

Purpose: Central nervous system metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges.

Patients And Methods: Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKi-pretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve).

Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study.

Background: Several paediatric malignancies, including anaplastic large cell lymphoma (ALCL), inflammatory myofibroblastic tumour (IMT), neuroblastoma, and rhabdomyosarcoma, harbour activation of anaplastic lymphoma kinase (ALK) through different mechanisms. Here, we report the safety, pharmacokinetics, and efficacy of ceritinib in paediatric patients with ALK-positive malignancies.

Methods: This multicentre, open-label, phase 1 trial was done at 23 academic hospitals in ten countries.

Role of Pv-aCO gradient and Pv-aCO/Ca-vO ratio during cardiac surgery: a retrospective observational study.

Introduction: Arterial lactate, mixed venous O saturation, venous minus arterial CO partial pressure (PCO) and the ratio between this gradient and the arterial minus venous oxygen content (PCO/CO) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of PCO and PCO/CO, and the interchangeability of the variables calculated from mixed and central venous samples.

Methods: 35 cardiac surgery patients were included.

Clinical and epidemiological features of tuberculosis isolated from critically ill patients.

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed.

Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen .

Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of , a basidiomycete that causes life-threatening meningoencephalitis in immunocompromised individuals.

Effect of ceritinib on the pharmacokinetics of coadministered CYP3A and 2C9 substrates: a phase I, multicenter, drug-drug interaction study in patients with ALK + advanced tumors.

Purpose: Ceritinib is an ALK receptor tyrosine kinase inhibitor approved as first- and second-line treatment in adult patients with ALK + metastatic non-small cell lung cancer (NSCLC). The study investigated the drug-drug interaction (DDI) potential of ceritinib when coadministered with midazolam and warfarin as probe substrates for CYP3A and CYP2C9 activity, respectively.

Methods: This was a phase I, multicenter, open-label, single sequence, crossover DDI study in 33 adult patients with ALK + NSCLC or other advanced tumors.

Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with : More Is Not Necessarily Better.

Most people infected with the fungus spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.

Development and validation of an LC-MS/MS method for the quantitative analysis of the adenosine A2a receptor antagonist NIR178 and its monohydroxy metabolite in human plasma: Application to clinical pharmacokinetics.

We report a selective LC-MS/MS method for the simultaneous quantitative determinations of the adenosine A2a receptor antagonist NIR178 (NIR178) and its major metabolite NJI765 in human plasma. Sample preparation steps involved protein precipitation, sample evaporation and reconstitution using a plasma sample volume of 0.1 ml plasma.

Analysis of NAC Domain Transcription Factor Genes of L.f. Involved in Secondary Cell Wall Deposition.

NAC proteins are one of the largest families of plant-specific transcription factors (TFs). They regulate diverse complex biological processes, including secondary xylem differentiation and wood formation. Recent genomic and transcriptomic studies of L.

A hidden battle in the dirt: Soil amoebae interactions with Paracoccidioides spp.

Paracoccidioides spp. are thermodimorphic fungi that cause a neglected tropical disease (paracoccidioidomycosis) that is endemic to Latin America. These fungi inhabit the soil, where they live as saprophytes with no need for a mammalian host to complete their life cycle.

The structure of a prokaryotic viral envelope protein expands the landscape of membrane fusion proteins.

Lipid membrane fusion is an essential function in many biological processes. Detailed mechanisms of membrane fusion and the protein structures involved have been mainly studied in eukaryotic systems, whereas very little is known about membrane fusion in prokaryotes. Haloarchaeal pleomorphic viruses (HRPVs) have a membrane envelope decorated with spikes that are presumed to be responsible for host attachment and membrane fusion.

The Ferric uptake regulator (Fur) and iron availability control the production and maturation of the antibacterial peptide microcin E492.

Microcin E492 is a pore-forming bacteriocin with toxic activity against Enterobacteriaceae, which undergoes amyloid aggregation as a mechanism to regulate its toxicity. To be active, it requires the posttranslational attachment to the C-terminus of a glycosylated enterochelin derivative (salmochelin), a process carried out by the proteins MceC, MceI and MceJ encoded in the MccE492 gene cluster. Both microcin E492 and salmochelin have a proposed role in the virulence of the bacterial pathogen Klebsiella pneumoniae.

Statistical analysis plan for early goal-directed therapy using a physiological holistic view - the ANDROMEDA-SHOCK: a randomized controlled trial.

Background: ANDROMEDA-SHOCK is an international, multicenter, randomized controlled trial comparing peripheral perfusion-targeted resuscitation to lactate-targeted resuscitation in patients with septic shock in order to test the hypothesis that resuscitation targeting peripheral perfusion will be associated with lower morbidity and mortality.

Objective: To report the statistical analysis plan for the ANDROMEDA-SHOCK trial.

Methods: We describe the trial design, primary and secondary objectives, patients, methods of randomization, interventions, outcomes, and sample size.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

Background: Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients.

Development and Qualification of a Drug-Disease Modeling Platform to Characterize Clinically Relevant Endpoints in Type 2 Diabetes Trials.

Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease characterized by persistently elevated blood glucose concentration (hyperglycemia). We developed a mechanistic drug-disease modeling platform based on data from more than 4,000 T2DM subjects in seven phase II/III clinical trials. The model integrates longitudinal changes in clinically relevant biomarkers of glycemic control with information on baseline disease state, demographics, disease progression, and different therapeutic interventions, either when given alone or as add-on combination therapy.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

Background: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients.

Bacterial Tubulins A and B Exhibit Polarized Growth, Mixed-Polarity Bundling, and Destabilization by GTP Hydrolysis.

Bacteria of the genus express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB (BtubA/B), that have been observed to assemble into filaments in the presence of GTP. BtubA/B polymers are proposed to be composed by two to six protofilaments in contrast to that , where they have been reported to form 5-protofilament tubes named bacterial microtubules (bMTs). The genes likely entered the lineage via horizontal gene transfer and may be derived from an early ancestor of the modern eukaryotic microtubule (MT).

Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin America: A Study From the Latin America Intensive Care Network.

Objective: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs.

Design: Web-based survey submitted to ICU directors.

Screening of the in vitro antileishmanial activities of compounds and secondary metabolites isolated from Maytenus guianensis Klotzsch ex Reissek (Celastraceae) chichuá Amazon.

Introduction: Maytenus guianensis is a member of the Celastraceae family that is used in traditional medicine, particularly for its anti-parasitic and anti-cancer effects. To explore the ethnopharmacological potential of this plant, the present study was designed to screen the in vitro antileishmanial activities of extracts and compounds isolated from M. guianensis.

Microcirculatory changes during cardiac surgery with cardiopulmonary bypass.

Objective: To evaluate microcirculation in intermediate and high mortality risk patients undergoing cardiac surgery (CS) with cardiopulmonary bypass (CPB).

Patients And Methods: The study included 22 patients with a Euroscore >3. Using the Videomicroscopy Side Stream Dark Field system, and evaluation was made of, capillary density, proportion of perfused capillaries, density of perfused capillaries, microcirculatory flow index (MFI), and heterogeneity flow index.

Effects of early hemodynamic resuscitation on left ventricular performance and microcirculatory function during endotoxic shock.

Background: Microcirculation and macrohemodynamics are severely compromised during septic shock. However, the relationship between these two compartments needs to be further investigated. We hypothesized that early resuscitation restores left ventricular (LV) performance and microcirculatory function but fails to prevent metabolic disorders.