Publications by authors named "Lankelma J"

The orbitofrontal cortex, one of the key neocortical areas in valuation and emotion, is critical for cognitive flexibility but its role in the consolidation of recently acquired information remains unclear. Here, we demonstrate orbitofrontal offline replay in the context of a place-reward association task on a maze with varying goal locations. When switches in place-reward coupling were applied, replay was enhanced relative to sessions with stable contingencies.

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To define sensitivity and specificity of Vitek 2 MICs as phenotypic screening method for carbapenemase-producing . We determined Vitek 2 MICs of antipseudomonal antimicrobials in 130 unrelated carbapenemase-producing and 129 carbapenemase-negative isolates within a Dutch carbapenemase-surveillance database. We calculated test characteristics of single and combined antimicrobial MICs for carbapenemase production.

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Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. We employed multi-omics factor analysis (MOFA) to systematically integrate the bacterial (16S rRNA), fungal (intergenic transcribed spacer 1 rRNA), and viral (virus discovery next-generation sequencing) components of the intestinal microbiota of 33 critically ill patients with and without sepsis and 13 healthy volunteers.

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In order to make high-performance liquid chromatography (HPLC) more widely available at home and in small-scale settings, we have simplified two of its most costly modules, namely the pump and the detector. This should make the setup affordable for home or small laboratory use. A manual HPLC pump was constructed so as to fit into a caulk gun from a local hardware store enabling the generation of 100-150 bar of pressure.

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Background: An increasing body of evidence is indicating that the gut microbiota modulates pulmonary inflammatory responses. This so-called gut-lung axis might be of importance in a whole spectrum of inflammatory pulmonary diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease and pneumonia. Here, we investigate the effect of antibiotic disruption of gut microbiota on immune responses in the lung after a intranasal challenge with lipopolysaccharide (LPS).

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Patients that suffer from sepsis exhibit an early hyper-inflammatory immune response which can lead to organ failure and death. In our study, we assessed the immune modulation in the human in vivo endotoxemia model and compared it to ex vivo LPS stimulation using 38 transcriptomic markers. Blood was collected before and after 4 hours of LPS challenge and tested with the Immune Profiling Panel (IPP) using the FilmArray system.

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A proportion of patients suspected of Clostridium difficile infection are unnecessarily placed in contact isolation. By introducing a random-access glutamate dehydrogenase (GDH) test for C. difficile, we aimed to reduce isolation time.

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The Gram-negative intracellular pathogen is the causative agent of melioidosis, an important cause of sepsis in Southeast Asia. Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is essential for an appropriate immune response during pathogen invasion. In patients with melioidosis, TLR5 is the most abundantly expressed TLR, and a hypofunctional TLR5 variant has been associated with improved survival.

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Background: The seasonal influenza epidemic poses a significant burden on hospitals, both in terms of capacity and costs. Beds that are occupied by isolated influenza patients result in hospitals temporary being closed to admissions and elective operations being cancelled. Improving hospital and emergency department (ED) patient flow during the influenza season could solve these problems.

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Objectives: The impact of combination antibiotic therapy on the composition of the intestinal microbiota remains ill-defined. We aimed to assess the effect of a 1 week antibiotic regimen on the intestinal microbiota of healthy humans for a period of up to 31 months.

Patients And Methods: Thirteen healthy adult men received either no treatment or oral broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days.

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Peptidylarginine deiminase 4 (PAD4) catalyzes citrullination of histones, an important step for neutrophil extracellular trap (NET) formation. We aimed to determine the role of PAD4 during pneumonia. Markers of NET formation were measured in lavage fluid from airways of critically ill patients.

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Cognitive challenges are often accompanied by a discharge of stress hormones, which in turn modulate multiple brain areas. Among these, the medial temporal lobe and the prefrontal cortex are critically involved in high-order cognitive functions such as learning, memory, and decision-making. Previous studies assessing the effects of corticosterone on spatial memory found an increase or a decrease in performance depending on the timing of stress hormone discharge relative to the behavioral task.

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Background: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. Here, we aimed to characterize the composition and function of the intestinal microbiota during experimental melioidosis.

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Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis.

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Purpose: The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting.

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Background: Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The NLRP3 inflammasome and its downstream product interleukin-1 beta (IL-1β) have been proposed to play crucial roles in melioidosis. In this study, we characterized the role of IL-1β more closely and we assessed its therapeutic potential.

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Unlabelled: The use of information from the hippocampal memory system in motivated behavior depends on its communication with the ventral striatum. When an animal encounters cues that signal subsequent reward, its reward expectancy is raised. It is unknown, however, how this process affects hippocampal dynamics and their influence on target structures, such as ventral striatum.

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Objectives: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking.

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Unlabelled: Behavioral states are commonly considered global phenomena with homogeneous neural determinants. However, recent studies indicate that behavioral states modulate spiking activity with neuron-level specificity as a function of brain area, neuronal subtype, and preceding history. Although functional connectivity also strongly depends on behavioral state at a mesoscopic level and is globally weaker in non-REM (NREM) sleep and anesthesia than wakefulness, it is unknown how neuronal communication is modulated at the cellular level.

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Objective: The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens.

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Background: Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis.

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The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.

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Objective: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown.

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