Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation.

Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derived tumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contact hypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derived TNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while being dispensable for endothelial cell activation. The MC-derived TNF was infused into the bloodstream by directional degranulation of perivascular MCs that were part of the vascular unit with access to the vessel lumen. Consistently, intravenous administration of MC granules boosted neutrophil extravasation. Pronounced and rapid intravascular MC degranulation was also observed upon IgE crosslinking or LPs challenge indicating a universal MC potential. Consequently, the directional MC degranulation of pro-inflammatory mediators into the bloodstream may represent an important target for therapeutic approaches aimed at dampening cytokine storm syndromes or shock symptoms, or intentionally pushing immune defense.

Nitric oxide controls proliferation of Leishmania major by inhibiting the recruitment of permissive host cells.

Nitric oxide (NO) is an important antimicrobial effector but also prevents unnecessary tissue damage by shutting down the recruitment of monocyte-derived phagocytes. Intracellular pathogens such as Leishmania major can hijack these cells as a niche for replication. Thus, NO might exert containment by restricting the availability of the cellular niche required for efficient pathogen proliferation. However, such indirect modes of action remain to be established. By combining mathematical modeling with intravital 2-photon biosensors of pathogen viability and proliferation, we show that low L. major proliferation results not from direct NO impact on the pathogen but from reduced availability of proliferation-permissive host cells. Although inhibiting NO production increases recruitment of these cells, and thus pathogen proliferation, blocking cell recruitment uncouples the NO effect from pathogen proliferation. Therefore, NO fulfills two distinct functions for L. major containment: permitting direct killing and restricting the supply of proliferation-permissive host cells.

CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours.

Most clinically applied cancer immunotherapies rely on the ability of CD8+ cytolytic T cells to directly recognize and kill tumour cells1-3. These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment4-6. The ability of CD4+ effector cells to contribute to antitumour immunity independently of CD8+ T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified7-10. Here, we describe a mechanism whereby a small number of CD4+ T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting. The CD4+ effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II+CD11c+ antigen-presenting cells. We show that T helper type 1 cell-directed CD4+ T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4+ T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4+ T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8+ T cells and natural killer cells and advance cancer immunotherapies.

An open-access volume electron microscopy atlas of whole cells and tissues.

Understanding cellular architecture is essential for understanding biology. Electron microscopy (EM) uniquely visualizes cellular structures with nanometre resolution. However, traditional methods, such as thin-section EM or EM tomography, have limitations in that they visualize only a single slice or a relatively small volume of the cell, respectively. Focused ion beam-scanning electron microscopy (FIB-SEM) has demonstrated the ability to image small volumes of cellular samples with 4-nm isotropic voxels1. Owing to advances in the precision and stability of FIB milling, together with enhanced signal detection and faster SEM scanning, we have increased the volume that can be imaged with 4-nm voxels by two orders of magnitude. Here we present a volume EM atlas at such resolution comprising ten three-dimensional datasets for whole cells and tissues, including cancer cells, immune cells, mouse pancreatic islets and Drosophila neural tissues. These open access data (via OpenOrganelle2) represent the foundation of a field of high-resolution whole-cell volume EM and subsequent analyses, and we invite researchers to explore this atlas and pose questions.

Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy.

Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies. In the absence of c-MET inhibition, neutrophils recruited to T cell-inflamed microenvironments rapidly acquired immunosuppressive properties, restraining T cell expansion and effector functions. In cancer patients, high serum levels of the c-MET ligand HGF correlated with increasing neutrophil counts and poor responses to checkpoint blockade therapies. Our findings reveal a role for the HGF/c-MET pathway in neutrophil recruitment and function and suggest that c-MET inhibitor co-treatment may improve responses to cancer immunotherapy in settings beyond c-MET-dependent tumors.

Investigating pyroptosis as a mechanism of L. major cell-to-cell spread in the human BLaER1 infection model.

Leishmania is the causative agent of the tropical neglected disease leishmaniasis and infects macrophages as its definitive host cell. In order to sustain and propagate infections, Leishmania parasites have to complete cycles of exit and re-infection. Yet, the mechanism driving the parasite spread to other cells remains unclear. Recent studies reported pro-inflammatory monocytes as replicative niche of Leishmania major and showed prolonged expression of IL-1ß at the site of infection, indicating an activation of the NLRP3 inflammasome and pointing toward pyroptosis as a possible mechanism of parasite spread. To address the species-specific inflammasome activation of human cells, we characterized the BLaER1 monocytes as a model for L. major infection. We found that BLaER1 monocytes support infection and activation by Leishmania parasites to the same extent as primary human macrophages. Harnessing the possibilities of this infection model, we first showed that BLaER1 GSDMD-/- cells, which carry a deletion of the pore-forming protein gasdermin D, are more resistant to pyroptotic cell death and, concomitantly, display a strongly delayed release of intracellular parasite. Using that knockout in a co-incubation assay in comparison with wild-type BLaER1 cells, we demonstrate that impairment of the pyroptosis pathway leads to lower rates of parasite spread to new host cells, thus, implicating pyroptotic cell death as a possible exit mechanism of L. major in pro-inflammatory microenvironments.

Fully automatic algorithm for detecting and tracking anatomical shoulder landmarks on fluoroscopy images with artificial intelligence.

OBJECTIVE: Patients with rotator cuff tears present often with glenohumeral joint instability. Assessing anatomic angles and shoulder kinematics from fluoroscopy requires labelling of specific landmarks in each image. This study aimed to develop an artificial intelligence model for automatic landmark detection from fluoroscopic images for motion tracking of the scapula and humeral head. MATERIALS AND METHODS: Fluoroscopic images were acquired for both shoulders of 25 participants (N = 12 patients with unilateral rotator cuff tear, 6 men, mean (standard deviation) age: 63.7 ± 9.7 years; 13 asymptomatic subjects, 7 men, 58.2 ± 8.9 years) during a 30° arm abduction and adduction movement in the scapular plane with and without handheld weights of 2 and 4 kg. A 3D full-resolution convolutional neural network (nnU-Net) was trained to automatically locate five landmarks (glenohumeral joint centre, humeral shaft, inferior and superior edges of the glenoid and most lateral point of the acromion) and a calibration sphere. RESULTS: The nnU-Net was trained with ground-truth data from 6021 fluoroscopic images of 40 shoulders and tested with 1925 fluoroscopic images of 10 shoulders. The automatic landmark detection algorithm achieved an accuracy above inter-rater variability and slightly below intra-rater variability. All landmarks and the calibration sphere were located within 1.5 mm, except the humeral landmark within 9.6 mm, but differences in abduction angles were within 1°. CONCLUSION: The proposed algorithm detects the desired landmarks on fluoroscopic images with sufficient accuracy and can therefore be applied to automatically assess shoulder motion, scapular rotation or glenohumeral translation in the scapular plane. CLINICAL RELEVANCE STATEMENT: This nnU-net algorithm facilitates efficient and objective identification and tracking of anatomical landmarks on fluoroscopic images necessary for measuring clinically relevant anatomical configuration (e.g. critical shoulder angle) and enables investigation of dynamic glenohumeral joint stability in pathological shoulders. KEY POINTS: • Anatomical configuration and glenohumeral joint stability are often a concern after rotator cuff tears. • Artificial intelligence applied to fluoroscopic images helps to identify and track anatomical landmarks during dynamic movements. • The developed automatic landmark detection algorithm optimised the labelling procedures and is suitable for clinical application.

Outbreak of severe community-acquired bacterial infections among children in North Rhine-Westphalia (Germany), October to December 2022.

PURPOSE: In late 2022, a surge of severe S. pyogenes infections was reported in several European countries. This study assessed hospitalizations and disease severity of community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in North Rhine-Westphalia (NRW), Germany, during the last quarter of 2022 compared to long-term incidences. METHODS: Hospital cases due to bacterial infections between October and December 2022 were collected in a multicenter study (MC) from 59/62 (95%) children's hospitals in NRW and combined with surveillance data (2016-2023) from the national reference laboratories for streptococci, N. meningitidis, and H. influenzae. Overall and pathogen-specific incidence rates (IR) from January 2016 to March 2023 were estimated via capture-recapture analyses. Expected annual deaths from the studied pathogens were calculated from national death cause statistics. RESULTS: In the MC study, 153 cases with high overall disease severity were reported with pneumonia being most common (59%, n = 91). IRs of bacterial infections declined at the beginning of the COVID-19 pandemic and massively surged to unprecedented levels in late 2022 and early 2023 (overall hospitalizations 3.5-fold), with S. pyogenes and S. pneumoniae as main drivers (18-fold and threefold). Observed deaths during the study period exceeded the expected number for the entire year in NRW by far (7 vs. 0.9). DISCUSSION: The unprecedented peak of bacterial infections and deaths in late 2022 and early 2023 was caused mainly by S. pyogenes and S. pneumoniae. Improved precautionary measures are needed to attenuate future outbreaks.

Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.

ß cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of ß cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo-labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.

Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment.

PURPOSE: In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group. METHODS: We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group. RESULTS: In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = - 74.04, T = - 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological. CONCLUSION: NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

Active control of target sound fields using structural-acoustic brightness applied to a ship model's acoustic signature.

This manuscript presents a method for reproducing sound fields actively by using a vibrating submerged structure as the field reproduction source, with the target sound field to be reproduced defined in the frequency domain using the acoustic brightness approach. To balance the predetermination of a mono- or multi-zone target sound pressure field and the control effort required, singular value decomposition of the structural-acoustic system matrix is proposed. The dependency of the radiation efficiency into the target zone on the singular modes representing source and pressure modes is investigated using a wavenumber-domain approach. Furthermore, a feedforward control principle is adopted for adaptive sound-field reproduction with mode matching from the least squares perspective. Finally, an experiment is reported that involve synthesizing a tonal target underwater acoustic signature of a model of a fast attack craft (scale 1:8) at a measurement facility at Lake Plön in Germany. The results show that with the structural-acoustic brightness approach structural modes with radiation coupling into the target zone are excited and related pressure modes exhibit individual focus in the direction of hydrophones in use. Finally, a predetermined narrowband sound pressure field is actively reproduced at the hydrophone positions using inertial actuators and accelerometers on the ship model's hull.

ChatGPT-4 generates orthopedic discharge documents faster than humans maintaining comparable quality: a pilot study of 6 cases.

BACKGROUND AND PURPOSE: Large language models like ChatGPT-4 have emerged. They hold the potential to reduce the administrative burden by generating everyday clinical documents, thus allowing the physician to spend more time with the patient. We aimed to assess both the quality and efficiency of discharge documents generated by ChatGPT-4 in comparison with those produced by physicians. PATIENTS AND METHODS: To emulate real-world situations, the health records of 6 fictional orthopedic cases were created. Discharge documents for each case were generated by a junior attending orthopedic surgeon and an advanced orthopedic resident. ChatGPT-4 was then prompted to generate the discharge documents using the same health record information. The quality assessment was performed by an expert panel (n = 15) blinded to the source of the documents. As secondary outcome, the time required to generate the documents was compared, logging the duration of the creation of the discharge documents by the physician and by ChatGPT-4. RESULTS: Overall, both ChatGPT-4 and physician-generated notes were comparable in quality. Notably, ChatGPT-4 generated discharge documents 10 times faster than the traditional method. 4 events of hallucinations were found in the ChatGPT-4-generated content, compared with 6 events in the human/physician produced notes. CONCLUSION: ChatGPT-4 creates orthopedic discharge notes faster than physicians, with comparable quality. This shows it has great potential for making these documents more efficient in orthopedic care. ChatGPT-4 has the potential to significantly reduce the administrative burden on healthcare professionals.

[Ruptured pulmonary Echinococcus granulosus cyst: A rare cause of severe pneumogenic sepsis]. / Rupturierte pulmonale Echinococcus granulosus-Zyste ­ Eine seltene Ursache für eine schwere pneumogene Sepsis.

Parasitic infections by Echinococcus granulosus are rare in Germany, and predominantly affect individuals with a migration background. Liver and lungs are the most commonly affected organs. Pulmonary cysts often remain asymptomatic until rupture, at which point symptoms may manifest. The diagnostic approach typically involves a combination of imaging modalities and serological tests, occasionally supplemented by molecular genetic methods. Given the global movements of migration, considerations of the epidemiology of common diseases in the country of origin should also be taken into account in the differential diagnosis. We present the unusual case of a pneumogenic sepsis in a young man from Syria, where the combination of medical history alongside radiological, serological, and molecular genetic investigations ultimately led to the diagnosis of a severe pulmonary echinococcosis with rupture.

Severity of rotator cuff disorders and additional load affect fluoroscopy-based shoulder kinematics during arm abduction.

BACKGROUND: Rotator cuff disorders, whether symptomatic or asymptomatic, may result in abnormal shoulder kinematics (scapular rotation and glenohumeral translation). This study aimed to investigate the effect of rotator cuff tears on in vivo shoulder kinematics during a 30° loaded abduction test using single-plane fluoroscopy. MATERIALS AND METHODS: In total, 25 younger controls, 25 older controls and 25 patients with unilateral symptomatic rotator cuff tears participated in this study. Both shoulders of each participant were analysed and grouped on the basis of magnetic resonance imaging into healthy, rotator cuff tendinopathy, asymptomatic and symptomatic rotator cuff tears. All participants performed a bilateral 30° arm abduction and adduction movement in the scapular plane with handheld weights (0, 2 and 4 kg) during fluoroscopy acquisition. The range of upward-downward scapular rotation and superior-inferior glenohumeral translation were measured and analysed during abduction and adduction using a linear mixed model (loads, shoulder types) with random effects (shoulder ID). RESULTS: Scapular rotation was greater in shoulders with rotator cuff tendinopathy and asymptomatic rotator cuff tears than in healthy shoulders. Additional load increased upward during abduction and downward during adduction scapular rotation (P < 0.001 in all groups but rotator cuff tendinopathy). In healthy shoulders, upward scapular rotation during 30° abduction increased from 2.3° with 0-kg load to 4.1° with 4-kg load and on shoulders with symptomatic rotator cuff tears from 3.6° with 0-kg load to 6.5° with 4-kg load. Glenohumeral translation was influenced by the handheld weights only in shoulders with rotator cuff tendinopathy (P ≤ 0.020). Overall, superior glenohumeral translation during 30° abduction was approximately 1.0 mm with all loads. CONCLUSIONS: The results of glenohumeral translation comparable to control but greater scapular rotations during 30° abduction in the scapular plane in rotator cuff tears indicate that the scapula compensates for rotator cuff deficiency by rotating. Further analysis of load-dependent joint stability is needed to better understand glenohumeral and scapula motion. LEVEL OF EVIDENCE: Level 2. TRIAL REGISTRATION: Ethical approval was obtained from the regional ethics committee (Ethics Committee Northwest Switzerland EKNZ 2021-00182), and the study was registered at clinicaltrials.gov on 29 March 2021 (trial registration number NCT04819724, https://clinicaltrials.gov/ct2/show/NCT04819724 ).

Genomic characterization of a nematode tolerance locus in sugar beet.

BACKGROUND: Infection by beet cyst nematodes (BCN, Heterodera schachtii) causes a serious disease of sugar beet, and climatic change is expected to improve the conditions for BCN infection. Yield and yield stability under adverse conditions are among the main breeding objectives. Breeding of BCN tolerant sugar beet cultivars offering high yield in the presence of the pathogen is therefore of high relevance. RESULTS: To identify causal genes providing tolerance against BCN infection, we combined several experimental and bioinformatic approaches. Relevant genomic regions were detected through mapping-by-sequencing using a segregating F2 population. DNA sequencing of contrasting F2 pools and analyses of allele frequencies for variant positions identified a single genomic region which confers nematode tolerance. The genomic interval was confirmed and narrowed down by genotyping with newly developed molecular markers. To pinpoint the causal genes within the potential nematode tolerance locus, we generated long read-based genome sequence assemblies of the tolerant parental breeding line Strube U2Bv and the susceptible reference line 2320Bv. We analyzed continuous sequences of the potential locus with regard to functional gene annotation and differential gene expression upon BCN infection. A cluster of genes with similarity to the Arabidopsis thaliana gene encoding nodule inception protein-like protein 7 (NLP7) was identified. Gene expression analyses confirmed transcriptional activity and revealed clear differences between susceptible and tolerant genotypes. CONCLUSIONS: Our findings provide new insights into the genomic basis of plant-nematode interactions that can be used to design and accelerate novel management strategies against BCN.

Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study.

BACKGROUND AND AIMS: Fecal incontinence (FI) improvement following injection of autologous skeletal muscle-derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. METHODS: Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. RESULTS: Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. CONCLUSIONS: Injection of a high dose of autologous skeletal muscle-derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).

Physical activity and brain health in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated. METHODS: Patients from the multicenter Swiss-AF cohort study were included in this cross-sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score. RESULTS: Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62-0.99, p = 0.04), higher brain volume (ß-coefficient = 10.73, 95% CI = 2.37-19.09, p = 0.01), and higher CoCo score (ß-coefficient = 0.08, 95% CI = 0.03-0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (ß-coefficient = 1.40, 95% CI = 0.65-2.15, p < 0.001). CONCLUSIONS: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active.

Prevalence of Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa in orphans and street children in Mwanza city, Northern Tanzania.

BACKGROUND: Parasitic infections are highly prevalent in low-income environments worldwide. While orphans and street children represent a particularly vulnerable population group, they are often exempt from preventive interventions such as Mass Drug Administration. In part, this could be due to a lack of data showing the burden of disease in this group. This study aims to address this gap. METHODS: For this cross-sectional study, 144 orphans and 112 street children were screened for Schistosoma mansoni (S. mansoni), Schistosoma haematobium (S. haematobium), soil-transmitted helminths and intestinal protozoa using POC-CCA testing, urine filtration, and Kato-Katz technique. Nutritional status, water- and washing patterns were determined using a standardised questionnaire. Ultrasonography was performed to screen for organ abnormalities. RESULTS: The prevalence of S. mansoni determined by POC-CCA-test was 65.9% for orphans and 94.5% for street children. 19.2% of the orphans tested positive for S. mansoni in Kato Katz. Of the street children, 77.1% showed positive test results in Kato-Katz. Only 1.3% of the orphans stated in the questionnaire that they use the lake to wash, whereas 91.1% of the street children named the lake as at least one of their options for washing. Microscopy showed positive results for Giardia intestinalis (G. intestinalis) in 8.2% and for Entamoeba histolytica/dispar (E. histolytica/dispar) in 23% of orphans and 8.1% for G. intestinalis, and 23.8% for E. histolytica/dispar in street children. In the ultrasonography, we did not observe patterns that indicate severe periportal fibrosis. CONCLUSION: The results indicate a significantly higher rate of infections with S. mansoni in street children compared with orphans. This might be explained by the lack of access to adequate sanitation for street children as well as regular contact with the water of Lake Victoria. However, we did not find similar results concerning infection rates with protozoa. The study results show overall inadequate living conditions in this study population, which could be addressed by public health interventions.

femtoPro: virtual-reality interactive training simulator of an ultrafast laser laboratory.

The huge field of optics and photonics research and development is in constant demand of well-trained experts. However, it is challenging to teach efficiently the setup process of complicated optical experiments due to limited hardware availability and eye-safety concerns, in particular, in the case of femtosecond lasers. We have developed an interactive simulation of an ultrafast laser laboratory ("femtoPro") for teaching and training, implementing physical models for the calculation and visualization of Gaussian laser beam propagation, ultrashort optical pulses, their modulation by typical optical elements, and linear as well as nonlinear light-matter interaction. This facilitates the setup and simulated measurement procedure, in virtual reality (VR) and at real-time speeds, of various typical optical arrangements and spectroscopy schemes such as telescopes, interferometers, or pulse characterization. femtoPro can be employed to supplement academic teaching in connection with regular courses in optics or spectroscopy, to train future scientists and engineers in the field of (ultrafast) optics in practical skills, to communicate to other researchers how to set up and align a particular experiment, to "test-build" and simulate new designs of optical setups, to simulate ultrafast spectroscopy data, to offer practical exercises to high-school students, and to reach out to the general public.

Development of the WHO eye care competency framework.

BACKGROUND: The eye care workforce, particularly in lower resource settings, face challenges of limited integration into the health system, limited workforce capacity, mismatch of workforce to population need and poor quality of care. In recognition of these challenges, coupled with a gap in existing tools, provides a strong rationale for the development of the Eye care competency framework (ECCF). METHODS: A mixed methods approach was utilised to develop and validate the ECCF. Content was developed by extracting relevant components of existing frameworks used both within and outside of eye care. A diverse technical working group provided feedback and guidance on the structure, design, and content to create a preliminary draft. Competencies and activities were validated using a modified-Delphi study, and the framework was then piloted at four sites to understand how the tool can be implemented in different settings. RESULTS: The final version of the ECCF included eight outcomes, nine guiding principles, and content of each of the key elements, including the six domains, 22 competencies, 21 activities, 193 behaviours and 234 tasks, and the knowledge and skills that underpin them. 95/112 participants from the six WHO regions completed the modified-Delphi study, yielding an average of 96% agreement across the competencies and activities in the ECCF. The pilot showcased the versatility and flexibility of the ECCF, where each of the four sites had a different experience in implementing the ECCF. All sites found that the ECCF enabled them to identify gaps within their current workforce documentation. CONCLUSIONS: The ECCF was developed using a collaborative approach, reflecting the opinions of participants and stakeholders from all around the world. The comprehensive competencies and activities developed in the ECCF encompass the diverse roles of eye care workers, and thus encourage multi-disciplinary care and better integration into the health system. It is recommended that eye care workforce planners and developers use the ECCF, and adapt it to their context, to support workforce development and focus on the quality and scope of eye care service provision.