Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Allogeneic mesenchymal stromal/stem cell (MSC) infusions are a promising potential treatment for steroid-resistant aGvHD. Data from our institution and others demonstrate rescue of approximately 40-50% of aGvHD patients with MSCs in Phase I, II studies and minor side effects. Although promising, better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment. METHODS: Single cell human small intestine organoids were embedded in Matrigel, grown for 5 days and treated with busulfan for 48 h. Organoids damaged by treatment with busulfan or control organoids were co-cultured with 5000, 10,000, and 50,000 MSCs for 24 h, 48 h or 7 days and the analyses such as surface area determination, proliferation and apoptosis assessment, RNA sequencing and proteomics were performed. RESULTS: Here, we developed a 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating epithelial to mesenchymal transition, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan-treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis. CONCLUSIONS: Collectively, we demonstrate that our in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium. This could benefit further optimization of the use of MSCs in HSCT patients.

Evaluation of colour vision impairment during acute hypobaric hypoxia in aviation medicine: a randomized controlled trial.

The digitization of aircraft cockpits places high demands on the colour vision of pilots. The present study investigates colour vision changes upon acute exposure to hypobaric hypoxia. The digital Waggoner Computerized Color Vision Test and the Waggoner D-15 were performed by 54 healthy volunteers in a decompression chamber. Respective altitude levels were sea level, 10,000 or 15,000 ft for exposure periods of 15 and 60 min, respectively. As for 60 min of exposure a significant decrease in colour perception was found between subjects at 15,000 ft as compared to the control group as well as between subjects at 15,000 ft as compared to subjects at 10,000 ft. No significant difference was found in the comparison within the 15,000 ft groups across time points pre-, peri-, and post-exposure. Thus, pilots appear to experience only minor colour vision impairment up to an exposure altitude of 15,000 ft over 60 min of exposure.

Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

Assessing the agreement between the pneumatic and the flow-centrifuge method for estimating xylem safety in temperate diffuse-porous tree species.

The increasing frequency of global change-type droughts has created a need for fast, accurate and widely applicable techniques for estimating xylem embolism resistance to improve forecasts of future forest changes. We used data from 12 diffuse-porous temperate tree species covering a wide range of xylem safety to compare the pneumatic and flow-centrifuge method, two rapid methods used for constructing xylem vulnerability curves. We evaluated the agreement between parameters estimated with both methods and the sensitivity of pneumatic measurements to the duration of air discharge (AD) measurements. There was close agreement between xylem water potentials at 50% air discharged (PAD), estimated with the Pneumatron, and 50% loss of hydraulic conductivity (PLC), estimated with the flow-centrifuge method (mean signed deviation: 0.12 MPa, Pearson correlation: 0.96 after 15 s of gas extraction). However, the relationship between the estimated slopes was more variable, resulting in lower agreement in the xylem water potential at 12% and 88% PAD/PLC. The agreement between the two methods was not affected by species-specific vessel length distributions. All pneumatic parameters were sensitive to AD time. Overall agreement was highest at relatively short AD times, with an optimum at 16 s. Our results highlight the value of the Pneumatron as an easy and reliable tool to estimate 50% embolism thresholds for a wide range of diffuse-porous temperate angiosperms. Further, our study provides a set of useful metrics for methodological comparisons of vulnerability curves in terms of systematic and random deviations, as well as overall agreement.

Influence of transition from open bay units to single room units in a neonatal intensive care unit on hospital transmission of multi-drug-resistant Enterobacterales.

BACKGROUND: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital. METHODS: This retrospective cohort study included all infants carrying MDROs admitted to the NICU of a tertiary care academic hospital 2 years prior to the transition from OBUs to SRUs in May 2017, and 1.5 years after the transition (2018-2020). RESULTS: In total, 55 infants were diagnosed with MDRO carriership. Isolates were available from 49 infants for cgMLST. In the OBU period, one cluster involving four of 20 (20%) infants was identified, and in the SRU period, four clusters involving nine of 29 (31%) infants were identified. It was possible to make an epidemiological link in all four SRU MDRO clusters, but this was not possible for the OBU cluster. In the latter case, transmission from an environmental source on the ward seemed likely. CONCLUSION: After transition to SRUs, there was no decrease in the number of clusters of MDROs with an epidemiological link, suggesting that nursing infants in an NICU with an SRU design is not, in itself, protective against the acquisition of MDROs.

Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort.

PURPOSES: Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. METHODS: All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). RESULTS: Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6-24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. CONCLUSIONS: This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent 'cure' proportions of surgery for rHPT but stretches the importance of long-term follow-up.

Possible alleviation of symptoms and side effects through clinicians' nocebo information and empathy in an experimental video vignette study.

To alleviate anti-cancer treatment burden in advanced breast cancer, patient-clinician communication strategies based on nocebo-effect mechanisms are promising. We assessed distinct/combined effects on psychological outcomes (e.g. anxiety; main outcome) and side-effect expectations of (1) nocebo information about the (non)pharmacological origin of side effects, and (2) clinician-expressed empathy through reassurance of continuing support. Furthermore, we explored whether information and empathy effects on side-effect expectations were mediated by decreased anxiety. In a two-by-two experimental video-vignette design, 160 cancer patients/survivors and healthy women watched one of four videos differing in level of nocebo information (±) and empathy (±). Regression and mediation analysis were used to determine effects of information/empathy and explore anxiety's mediating role. Anxiety was not influenced by empathy or information (Stai-state: p = 0.295; p = 0.390, VAS p = 0.399; p = 0.823). Information improved (specific) side-effect coping expectations (p < 0.01). Empathy improved side-effect intensity expectations (p < 0.01 = specific; p < 0.05 = non-specific/partial) and specific side-effect probability expectations (p < 0.01), and increased satisfaction, trust, and self-efficacy (p < 0.001). No mediating effects were found of anxiety on expectations. Mainly empathy, but also nocebo information improved psychological outcomes and-mainly specific-side-effect expectations. Exploring the power of these communication elements in clinical practice is essential to diminish the anti-cancer treatment burden in advanced breast cancer.

In situ Synthesis of Supramolecular Polymers: Finding the Right Conditions when Combining Covalent and Non-Covalent Synthesis.

The combination of covalent and non-covalent synthesis is omnipresent in nature and potentially enables access to new materials. Yet, the fundamental principles that govern such a synthesis are barely understood. Here, we demonstrate how even simple reaction mixtures behave surprisingly complex when covalent reactions are coupled to self-assembly processes. Specifically, we study the reaction behavior of a system in which the in situ formation of discotic benzene-1,3,5-tricarboxamide (BTA) monomers is linked to an intertwined non-covalent reaction network including self-assembly into helical BTA polymers. This system shows an unexpected phase-separation behavior in which an interplay of reactant/product concentrations, side-products and solvent purity determines the system composition. We envision that these insights can bring us one step closer to how to design the synthesis of systems in a combined covalent/non-covalent fashion.

Electroencephalography and psychological assessment datasets to determine the efficacy of a low-cost, wearable neurotechnology intervention for reducing Post-Traumatic Stress Disorder symptom severity.

The datasets described here comprise electroencephalography (EEG) data and psychometric data freely available on data.mendeley.com. The EEG data is available in .mat formatted files containing the EEG signal values structured in two-dimensional (2D) matrices, with channel data and trigger information in rows, and samples in columns (having a sampling rate of 250Hz). Twenty-nine female survivors of the 1994 genocide against the Tutsi in Rwanda, underwent a psychological assessment before and after an intervention aimed at reducing Post-Traumatic Stress Disorder (PTSD) symptom severity. Three measures of trauma and four measures of wellbeing were assessed using empirically validated standardised assessments. The pre- and post- intervention psychometric data were analysed using non-parametric statistical methods and the post-intervention data were further evaluated according to diagnostic assessment rules to determine clinically relevant improvements for each group. The participants were assigned to a control group (CG, n = 9), a motor-imagery group (MI, n = 10), and a neurofeedback group (NF, n = 10). Participants in the latter two groups received Brain-Computer Interface (BCI) based training as a treatment intervention over a sixteen-day period, between the pre- and post- clinical interviews. The training involved presenting feedback visually via a videogame, based on real-time analysis of the EEG recorded data during the BCI-based treatment session. Participants were asked to regulate (NF) or intentionally modulate (MI) brain activity to affect/control the game.

Dietary risk assessment of selected organophosphorus and pyrethoid pesticide residues in fresh harvested tomatoes at Makambako Town, Njombe region, Tanzania.

This study aimed to assess the levels of selected pesticides residues in harvested tomatoes and their associated dietary risks to consumers at Makambako Town in Njombe region, Tanzania. Forty-two fresh tomatoes were sampled among tomato farmers during harvesting season and extraction of analytes was done using QuEChERS method and analysed by Gas Chromatography-Mass Spectrometer. Residues of chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin were alternatingly detected in 78.51% of samples. The average concentrations of residues were 0.014, 0.056, 0.003 and 0.2 mg/kg for chlorpyrifos, profenofos, gamma cyhalothrin and cypermethrin and were all below their respective Codex MRLs. The highest concentration was 0.718 mg/kg for cypermethrin, above the Codex MRL of 0.2 mg/kg. The hazard indexes indicate no potential health hazards to the general population due to the lifetime consumption of fresh tomatoes from the study area. Periodic monitoring of residue levels of pesticides in vegetable fruits, including tomatoes, is recommended.

Stem and leaf xylem of angiosperm trees experiences minimal embolism in temperate forests during two consecutive summers with moderate drought.

Drought events may increase the likelihood that the plant water transport system becomes interrupted by embolism. Yet our knowledge about the temporal frequency of xylem embolism in the field is frequently lacking, as it requires detailed, long-term measurements. We measured xylem embolism resistance and midday xylem water potentials during the consecutive summers of 2019 and 2020 to estimate maximum levels of embolism in leaf and stem xylem of ten temperate angiosperm tree species. We also studied vessel and pit membrane characteristics based on light and electron microscopy to corroborate potential differences in embolism resistance between leaves and stems. Apart from A. pseudoplatanus and Q. petraea, eight species experienced minimum xylem water potentials that were close to or below those required to initiate embolism. Water potentials corresponding to ca. 12% loss of hydraulic conductivity (PLC) could occur in six species, while considerable levels of embolism around 50% PLC were limited to B. pendula and C. avellana. There was a general agreement in embolism resistance between stems and leaves, with leaves being equally or more resistant than stems. Also, xylem embolism resistance was significantly correlated to intervessel pit membrane thickness (TPM ) for stems, but not to vessel diameter and total intervessel pit membrane surface area of a vessel. Our data indicate that low amounts of embolism occur in most species during moderate summer drought, and that considerable levels of embolism are uncommon. Moreover, our experimental and TPM data show that leaf xylem is generally no more vulnerable than stem xylem.

Impact of transition from open bay to single room design neonatal intensive care unit on multidrug-resistant organism colonization rates.

BACKGROUND: The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented. AIM: To examine the effect of single room unit (SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU. METHODS: Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017. Weekly cultures of throat and rectum were collected to screen for MDRO carriership. Incidence of colonization (percentage of all infants and incidence density per 1000 patient-days) with MDROs and 3G-CRB were compared between OBU and SRU periods. FINDINGS: Incidence analysis of 1293 NICU infants, identified 3.2% MDRO carriers (2.5% OBU, 4.0% SRU, not significant), including 2.3% extended-spectrum ß-lactamase-producing Enterobacterales carriers, and 18.6% 3G-CRB carriers (17% OBU, 20% SRU, not significant). No differences were found in MDRO incidence density per 1000 patient-days between infants admitted to OBU (1.56) compared to SRU infants (2.63). CONCLUSION: Transition in NICU design from open bay to SRUs was not associated with a reduction in colonization rates with MDROs or 3G-CRB in our hospital. Further research on preventing the acquisition and spread of resistant bacteria at high-risk departments such as the NICU, as well as optimal ward design, are needed.

Neurofeedback with low-cost, wearable electroencephalography (EEG) reduces symptoms in chronic Post-Traumatic Stress Disorder.

BACKGROUND: The study examines the effectiveness of both neurofeedback and motor-imagery brain-computer interface (BCI) training, which promotes self-regulation of brain activity, using low-cost electroencephalography (EEG)-based wearable neurotechnology outside a clinical setting, as a potential treatment for post-traumatic stress disorder (PTSD) in Rwanda. METHODS: Participants received training/treatment sessions along with a pre- and post- intervention clinical assessment, (N = 29; control n = 9, neurofeedback (NF, 7 sessions) n = 10, and motor-imagery (MI, 6 sessions) n = 10). Feedback was presented visually via a videogame. Participants were asked to regulate (NF) or intentionally modulate (MI) brain activity to affect/control the game. RESULTS: The NF group demonstrated an increase in resting-state alpha 8-12 Hz bandpower following individual training sessions, termed alpha 'rebound' (Pz channel, p = 0.025, all channels, p = 0.024), consistent with previous research findings. This alpha 'rebound', unobserved in the MI group, produced a clinically relevant reduction in symptom severity in NF group, as revealed in three of seven clinical outcome measures: PCL-5 (p = 0.005), PTSD screen (p = 0.005), and HTQ (p = 0.005). LIMITATIONS: Data collection took place in environments that posed difficulties in controlling environmental factors. Nevertheless, this limitation improves ecological validity, as neurotechnology treatments must be deployable outside controlled environments, to be a feasible technological treatment. CONCLUSIONS: The study produced the first evidence to support a low-cost, neurotechnological solution for neurofeedback as an effective treatment of PTSD for victims of acute trauma in conflict zones in a developing country.

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Rift Valley fever virus detection in susceptible hosts with special emphasis in insects.

Rift Valley fever phlebovirus (RVFV, Phenuiviridae) is an emerging arbovirus that can cause potentially fatal disease in many host species including ruminants and humans. Thus, tools to detect this pathogen within tissue samples from routine diagnostic investigations or for research purposes are of major interest. This study compares the immunohistological usefulness of several mono- and polyclonal antibodies against RVFV epitopes in tissue samples derived from natural hosts of epidemiologic importance (sheep), potentially virus transmitting insect species (Culex quinquefasciatus, Aedes aegypti) as well as scientific infection models (mouse, Drosophila melanogaster, C6/36 cell pellet). While the nucleoprotein was the epitope most prominently detected in mammal and mosquito tissue samples, fruit fly tissues showed expression of glycoproteins only. Antibodies against non-structural proteins exhibited single cell reactions in salivary glands of mosquitoes and the C6/36 cell pellet. However, as single antibodies exhibited a cross reactivity of varying degree in non-infected specimens, a careful interpretation of positive reactions and consideration of adequate controls remains of critical importance. The results suggest that primary antibodies directed against viral nucleoproteins and glycoproteins can facilitate RVFV detection in mammals and insects, respectively, and therefore will allow RVFV detection for diagnostic and research purposes.

Is accommodation a confounder in pupillometry research?

Much psychological research uses pupil diameter measurements to investigate the cognitive and emotional effects of visual stimuli. A potential problem is that accommodating at a nearby point causes the pupil to constrict. This study examined to what extent accommodation is a confounder in pupillometry research. Participants solved multiplication problems at different distances (Experiment 1) and looked at line drawings with different monocular depth cues (Experiment 2) while their pupil diameter, refraction, and vergence angle were recorded using a photorefractor. Experiment 1 showed that the pupils dilated while performing the multiplications, for all presentation distances. Pupillary constriction due to accommodation was not strong enough to override pupil dilation due to cognitive load. Experiment 2 showed that monocular depth cues caused a small shift in refraction in the expected direction. We conclude that, for the young student sample we used, pupil diameter measurements are not substantially affected by accommodation.

Calcicole behaviour of Callisthene fasciculata Mart., an Al-accumulating species from the Brazilian Cerrado.

Most aluminium (Al)-accumulating species are found on soils with high Al saturation and low Ca availability (Ca poor). Callisthene fasciculata Mart. (Vochysiaceae), however, is an Al-accumulating tree restricted to Ca-rich soils with low Al saturation in the Brazilian Cerrado savanna. Here we tested its calcicole behaviour, and the possible role of organic acids in detoxification of Al during the early stages of plant development. We assessed growth, dry mass, nutrients, Al and organic acids in seedlings grown for 50 days on two contrasting Cerrado soils; one with high Ca concentrations and low Al saturation and the other with low Ca availability and high Al saturation. Relative to plants on Ca-rich soil, plants on Ca-poor soil had necrotic spots and bronzing of leaves. Roots and shoots contained reduced concentrations of P and Cu, but higher concentrations of Fe, Al and citrate. Despite lower concentrations in the soil, Ca and Mg increased in shoots. Shoot concentrations of oxalate were also higher. We confirmed C. fasciculata as an Al-accumulating species with calcicole behaviour. The increased concentrations of organic acids in plants with higher Al accumulation suggest that high availability of soluble Al does not prevent occurrence of this species on soils with high Al saturation. Instead, the absence of C. fasciculata from Ca-poor soils is probably due to imbalances in tissue Fe, Cu and Zn imposed by this soil type.