Breakthrough Mpox outbreak investigation, the delicate balance between host immune response and viral immune escape.

BACKGROUND: Limited data is available on Mpox breakthrough infections. PURPOSE: Investigate a Mpox breakthrough outbreak in three vaccinated individuals. METHODS: Study participants provided informed consent. Serology testing was performed in one involved individual (ID-1) using an in-house assay detecting anti-orthopoxvirus IgG. Whole genome sequencing (WGS) was carried out and compared to the reference sequence ON563414.3 (https://www.ncbi.nlm.nih.gov/nuccore/ON563414.3/). RESULTS: Three individuals vaccinated with modified vaccinia Ankara-Bavaria Nordic contracted Mpox following one sexual intercourse event. One of them (ID-1) had received only one vaccine dose, while the other two were fully vaccinated. ID-1 presented to the sexual health clinic of the Universitair Ziekenhuis Brussel with proctitis related to Mpox. Despite one vaccination, serology testing Three months post vaccine showed absence of Mpox virus (MPXV) specific antibodies in ID-1. In contrast, two weeks following the sexual intercourse, seroconversion occurred. WGS of the isolated MPXV showed, compared to the reference sequence, a total of seven single nucleotide variants with four of them indicating protein amino-acid changes. CONCLUSION: Incomplete MPXV vaccination as well as MPXV variants might result in breakthrough infections. Preventive measures, such as MPVX vaccination, could maintain immunity in individuals with higher risk of MPXV infection, and might lower disease severity.

Land-use change in the past 40 years explains shifts in arthropod community traits.

Understanding how anthropogenic activities induce changes in the functional traits of arthropod communities is critical to assessing their ecological consequences. However, we largely lack comprehensive assessments of the long-term impact of global-change drivers on the trait composition of arthropod communities across a large number of species and sites. This knowledge gap critically hampers our ability to predict human-driven impacts on communities and ecosystems. Here, we use a dataset of 1.73 million individuals from 877 species to study how four functionally important traits of carabid beetles and spiders (i.e. body size, duration of activity period, tolerance to drought, and dispersal capacity) have changed at the community level across ~40 years in different types of land use and as a consequence of land use changes (that is, urbanisation and loss of woody vegetation) at the landscape scale in Switzerland. The results show that the mean body size in carabid communities declined in all types of land use, with particularly stronger declines in croplands compared to forests. Furthermore, the length of the activity period and the tolerance to drought of spider communities decreased in most land use types. The average body size of carabid communities in landscapes with increased urbanisation in the last ~40 years tended to decrease. However, the length of the activity period, the tolerance to drought, and the dispersal capacity did not change significantly. Furthermore, urbanisation promoted increases in the average dispersal capacities of spider communities. Additionally, urbanisation favoured spider communities with larger body sizes and longer activity periods. The loss of woody areas at the landscape level was associated with trait shifts to carabid communities with larger body sizes, shorter activity periods, higher drought tolerances and strongly decreased dispersal capacities. Decreases in activity periods and dispersal capacities were also found in spider communities. Our study demonstrates that human-induced changes in land use alter key functional traits of carabid and spider communities in the long term. The detected trait shifts in arthropod communities likely have important consequences for their functional roles in ecosystems.

Role of viable but non culturable cells in patients with cystic fibrosis in the era of highly effective modulator therapy.

BACKGROUND: Lung infections antibiotic treatment in Cystic Fibrosis patients (pwCF) is often complicated by bacterial persisters, including the so-called Viable but Non Culturable (VBNC) forms, live cells undetected by the routine cultural microbiological methods. This study investigated the occurrence of VBNC cells of five CF bacterial pathogens in 94 pwCF over one year and the possible associations with the patients' clinical features. METHODS: Sputum samples, recovered at routine visits and during exacerbation episodes, were analyzed for the presence of the five pathogens by both routine culture-based assays and species-specific qPCR. VBNC cells were estimated as the difference between molecular and cultural counts and their presence was matched with the clinical data in particular the therapeutic regimens. RESULTS: All but ten pwCF showed the presence of VBNC cells at least once during the study. Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus were the species most frequently found in the VBNC state. Only the former showed a significant association between chronic infection and VBNC cells presence; VBNC-MSSA positive patients significantly increased overtime. The presence of non culturable bacteria was generally concurrent with poor lung functionality and more frequent pulmonary exacerbations. No significant association with modulator treatment was evidenced. CONCLUSIONS: The obtained data demonstrated the overwhelming occurrence of bacterial VBNC cells in CF lung infections, warranting a constant monitoring of pwCF and underlining the need of implementing the routine culture-based assays with culture-independent techniques. This is pivotal to understand the CF bacterial population dynamics and to efficiently contrast the lung infection progression and worsening.

Minor head injury in anticoagulated patients: performance of biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in the detection of intracranial injury. A prospective observational study.

OBJECTIVES: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED. METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI. RESULTS: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively. CONCLUSIONS: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed.

The impact of the COVID-19 pandemic on gram-negative bacteria susceptibility patterns in respiratory samples of intensive care units in the Brussels Capital Region, 2010-2021.

BACKGROUND: The effect of the Coronavirus Disease 2019 (COVID-19) pandemic on gram-negative bacteria nonsusceptibility to antibiotics is unclear. METHODS: Between January 1, 2010, and December 31, 2021, the respiratory samples of intensive care unit patients at 3 University Hospitals in Brussels were retrieved. Based on the nonsusceptibility to antimicrobial classes, drug-resistance patterns were defined as multi-drug-resistant, extensively drug-resistant, and pan-drug-resistant. The study time frame was divided into 6 periods of 2 years each, and the impact of the COVID-19 pandemic (last period: 2020-2021) was assessed. RESULTS: During the current study, 10,577 samples were identified from 5,889 patients. While a significant augmentation of multi-drug-resistant isolates was noticed once comparing 2 prepandemic periods (2012-2013 and 2014-2015), all 3 patterns of nonsusceptibility significantly increased, comparing the years before and throughout the COVID-19 pandemic (2018-2019 and 2020-2021). Globally, the greatest increase in antimicrobial nonsusceptibility, comparing the last 2 periods, was reported for piperacillin-tazobactam (from 28% to 38%). Pseudomonas aeruginosa was the most isolated species, and the most involved in the appearance of resistance, with an augmentation of nonsusceptibility percentage to meropenem of 22% (from 25% to 47%), between the prepandemic and the pandemic periods. CONCLUSIONS: The COVID-19 pandemic was associated with increasing trends of antimicrobial resistance in respiratory samples of patients admitted to the intensive care units in university hospitals with well-implemented antibiotic stewardship programs.

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

BACKGROUND: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. MATERIALS AND METHODS: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. RESULTS: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. CONCLUSIONS: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.

Therapeutical strategies in cavitary legionnaires' disease, two cases from the field and a systematic review.

BACKGROUND: Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD. METHODS: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed. RESULTS: Two patients were found by the UZ Brussel's medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low. RESULT OF SYNTHESIS (CASE REPORTS): The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients. RESULT OF SYNTHESIS (GUIDELINES): Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses. CONCLUSION: To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.

Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19.

Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82-91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48-12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12-28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14-1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.

Conventional and Advanced Magnetic Resonance Imaging Assessment of Non-Enhancing Peritumoral Area in Brain Tumor.

The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed.

Pivotal role of multiphase computed tomography angiography for collateral assessment in patients with acute ischemic stroke.

The cerebral collateral circulation is the main compensatory mechanism that maintains the ischemic penumbra viable, the tissue at risk for infarction that can be saved if blood flow is restored by reperfusion therapies. In clinical practice, the extent of collateral vessels recruited after vessel occlusion can be easily assessed with computed tomography angiography (CTA) using two different techniques: single-phase CTA (sCTA) and multi-phase CTA (mCTA). Both these methodologies have demonstrated a high prognostic predictive value for prognosis due to the strong association between the presence of good collaterals and favorable radiological and clinical outcomes in patients with acute ischemic stroke (AIS). However, mCTA seems to be superior to sCTA in the evaluation of collaterals and a promising tool for identifying AIS patients who can benefit from reperfusion therapies. In particular, it has recently been proposed the use of mCTA eligibility criteria has been recently proposed for the selection of AIS patients suitable for endovascular treatment instead of the current accepted criteria based on CT perfusion. In this review, we analyzed the characteristics, advantages and disadvantages of sCTA and mCTA to better understand their fields of application and the potential of mCTA in becoming the method of choice to assess collateral extent in AIS patients.

The magnetic signal from trunk bark of urban trees catches the variation in particulate matter exposure within and across six European cities.

Biomagnetic monitoring increasingly is applied to assess particulate matter (PM) concentrations, mainly using plant leaves sampled in small geographical area and from a limited number of species. Here, the potential of magnetic analysis of urban tree trunk bark to discriminate between PM exposure levels was evaluated and bark magnetic variation was investigated at different spatial scales. Trunk bark was sampled from 684 urban trees of 39 genera in 173 urban green areas across six European cities. Samples were analysed magnetically for the Saturation isothermal remanent magnetisation (SIRM). The bark SIRM reflected well the PM exposure level at city and local scale, as the bark SIRM (i) differed between the cities in accordance with the mean atmospheric PM concentrations and (ii) increased with the cover of roads and industrial area around the trees. Furthermore, with increasing tree circumferences, the SIRM values increased, as a reflection of a tree age effect related to PM accumulation over time. Moreover, bark SIRM was higher at the side of the trunk facing the prevailing wind direction. Significant relationships between SIRM of different genera validate the possibility to combine bark SIRM from different genera to improve sampling resolution and coverage in biomagnetic studies. Thus, the SIRM signal of trunk bark from urban trees is a reliable proxy for atmospheric coarse to fine PM exposure in areas dominated by one PM source, as long as variation caused by genus, circumference and trunk side is taken into account.

Spatial mismatch between wild bee diversity hotspots and protected areas.

Wild bees are critical for multiple ecosystem functions but are currently threatened. Understanding the determinants of the spatial distribution of wild bee diversity is a major research gap for their conservation. We modeled wild bee α and ß taxonomic and functional diversity in Switzerland to uncover countrywide diversity patterns and determine the extent to which they provide complementary information, assess the importance of the different drivers structuring wild bee diversity, identify hotspots of wild bee diversity, and determine the overlap between diversity hotspots and the network of protected areas. We used site-level occurrence and trait data from 547 wild bee species across 3343 plots and calculated community attributes, including taxonomic diversity metrics, community mean trait values, and functional diversity metrics. We modeled their distribution with predictors describing gradients of climate, resource availability (vegetation), and anthropogenic influence (i.e., land-use types and beekeeping intensity). Wild bee diversity changed along gradients of climate and resource availability; high-elevation areas had lower functional and taxonomic α diversity, and xeric areas harbored more diverse bee communities. Functional and taxonomic ß diversities diverged from this pattern, with high elevations hosting unique species and trait combinations. The proportion of diversity hotspots included in protected areas depended on the biodiversity facet, but most diversity hotspots occurred in unprotected land. Climate and resource availability gradients drove spatial patterns of wild bee diversity, resulting in lower overall diversity at higher elevations, but simultaneously greater taxonomic and functional uniqueness. This spatial mismatch among distinct biodiversity facets and the degree of overlap with protected areas is a challenge to wild bee conservation, especially in the face of global change, and calls for better integrating unprotected land. The application of spatial predictive models represents a valuable tool to aid the future development of protected areas and achieve wild bee conservation goals.

Desajuste espacial entre los puntos calientes de diversidad de abejas silvestres y las áreas protegidas Resumen Las abejas silvestres son de suma importancia para muchas funciones ecosistémicas, pero hoy en día se encuentran amenazadas. Conservarlas requiere de investigación para entender las determinantes de su distribución espacial. Modelamos la diversidad funcional y taxonómica α y ß de las abejas silvestres en Suiza para revelar los patrones de diversidad en el país y determinar el grado al que proporcionan información complementaria. También analizamos la importancia de los diferentes impulsores que estructuran la diversidad de las abejas silvestres, identificamos puntos calientes para su diversidad y determinamos el traslape entre estos puntos calientes y la red de áreas protegidas. Usamos datos de los rasgos y la existencia a nivel de sitio de 547 especies de abejas silvestres en 3343 parcelas y calculamos los atributos comunitarios, incluyendo las medidas de diversidad taxonómica, los valores medios de las características de la comunidad y las medidas de diversidad funcional. Modelamos la distribución de las especies de abejas con indicadores que describieron las gradientes climáticas, de disponibilidad de recursos (vegetación) y de influencia antropogénica (es decir, tipos de uso de suelo e intensidad de apicultura). La diversidad de abejas silvestres cambió junto con los gradientes climáticos y de disponibilidad de recursos; las áreas elevadas tuvieron una diversidad funcional y taxonómica α más baja y las áreas xerófilas albergaron comunidades de abejas más diversas. Las diversidades funcional y taxonómica ß difirieron de este patrón pues las áreas elevadas albergaron especies y combinaciones de características únicas. La proporción de los puntos calientes de diversidad incluidos en las áreas protegidas dependieron de la faceta de la biodiversidad, aunque la mayoría de los puntos calientes se ubicaron en suelo no protegido. Los gradientes climáticos y de disponibilidad de recursos fueron factores en los patrones espaciales de la diversidad de abejas silvestres, lo que resultó en una diversidad general más baja en las áreas elevadas, pero a la vez con una mayor singularidad taxonómica y funcional. Este desfase espacial entre las diferentes facetas de la biodiversidad y el traslape con las áreas protegidas es un reto para la conservación de las abejas silvestres, especialmente de cara al cambio global, y requiere de una mejor integración del suelo no protegido. La aplicación de los modelos espaciales predictivos es una herramienta importante de apoyo para el desarrollo de áreas protegidas en el futuro y para lograr los objetivos de conservación de las abejas silvestres.

Diagnostic approach to monkeypox outbreak, a case-control study.

BACKGROUND: An international outbreak of the monkeypox (MPX) virus is ongoing with a different clinical presentation than previously reported. OBJECTIVE: A monocentric retrospective study was designed to investigate clinical predictors of confirmed MPX cases among a group of patients referred for MPX screening. Furthermore, the additional value of performing a real-time polymerase chain reaction (RT-PCR) on multiple anatomical sites was analyzed. METHODS: Between 28/05/2022 and 22/07/2022, the medical records of patients referred for MPX screening were investigated. Patients with positive RT-PCR were defined as cases, while the ones with negative RT-PCR as controls. Multivariable regression analysis was performed to estimate predictors of MPX diagnosis. RESULTS: Among the 141 included patients, 85 (60%) had at least one positive RT-PCR for MPX. Carrying out RT-PCR only on the swab obtained by skin lesion sampling, 7 patients (7/85: 8%) would have been misdiagnosed. Multivariable regression analysis showed significant differences in the independent variables: "being men who have sex with men (MSM)", "living with HIV", "having multiple sexual partners in the last 3 weeks", and "having skin lesions in the anogenital area" for prediction of MPX diagnosis. These four discriminants were used to create a score to improve diagnosis in patients screened for MPX. CONCLUSION: MPX diagnosis was associated with being MSM, living with HIV, having multiple sexual partners, and presenting with anogenital skin lesions. In this study, the derived score had good sensitivity and specificity to predict MPX diagnosis. Finally, performing multi-site swabs for MPX RT-PCR might lower false negative rates.

Features of post-obstructive pneumonia in advanced lung cancer patients, a large retrospective cohort.

BACKGROUND: Post-obstructive pneumonia refers to an infection of the lung parenchyma distal to a bronchial obstruction. Previous experience-based studies reported a high prevalence of this infection among patients with a medical history of advanced lung neoplasia, up to 40-55%. OBJECTIVES: The current study was designed to investigate the features of post-obstructive pneumonia in lung cancer, including its predictors and the discriminants for 30-day mortality. METHOD: Data from medical records at the tertiary University centre, UZ Brussel, were collected retrospectively between January 2016 and January 2021. Patients affected by lung cancer stages III and IV were included. A multidisciplinary team, composed of a pulmonologist, an infectious disease specialist and a chest radiologist, identified patients affected by post-obstructive pneumonia. RESULTS: A total of 408 patients were included, of which 46 (11%) were diagnosed with post-obstructive pneumonia. Multivariable logistic regression for predictors of disease onset found significant differences for squamous cell carcinoma (OR:2.46 p-value: .014) and hilar location of the tumour (OR:2.72 p-value: .021). However, no significant differences were identified with regards to age or comorbidities. Furthermore, 30-day mortality among post-obstructive pneumonia patients was 30%. Multivariable logistic regression for prediction of 30-day mortality found significant differences in CURB-65 score (OR:73.20 p-value: .001) and smoking status (OR:0.009 p-value: .015). CONCLUSIONS: Within this cohort, the prevalence of post-obstructive pneumonia in advanced lung cancer patients was lower than previously reported. Squamous cell carcinoma and a hilar tumour location were two variables associated with disease development, independent of age and comorbidities. Furthermore, a higher CURB-65 score at post-obstructive pneumonia diagnosis was correlated with mortality.

Early administration of tofacitinib in COVID-19 pneumonitis: An open randomised controlled trial.

BACKGROUND: Controversies on sub-populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID-19. OBJECTIVES: We designed a multicentre open-label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID-19 pneumonitis. METHODS: Patients admitted to three Italian hospitals affected by COVID-19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission. RESULTS: A total of 116 patients were randomised; 49 in the experimental arm completed the 14-day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SO2 > 93%, invasive mechanical ventilation or death by day 14 was 15.5%, significantly less than in the control group (20/58, 34.4%, RR 0,45, RRR -55%, NNT 5; p = .018). No differences in severe adverse effect incidence had been observed across the groups. CONCLUSION: High-dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.

A trait-based framework for dung beetle functional ecology.

Traits are key for understanding the environmental responses and ecological roles of organisms. Trait approaches to functional ecology are well established for plants, whereas consistent frameworks for animal groups are less developed. Here we suggest a framework for the study of the functional ecology of animals from a trait-based response-effect approach, using dung beetles as model system. Dung beetles are a key group of decomposers that are important for many ecosystem processes. The lack of a trait-based framework tailored to this group has limited the use of traits in dung beetle functional ecology. We review which dung beetle traits respond to the environment and affect ecosystem processes, covering the wide range of spatial, temporal and biological scales at which they are involved. Dung beetles show trait-based responses to variation in temperature, water, soil properties, trophic resources, light, vegetation structure, competition, predation and parasitism. Dung beetles' influence on ecosystem processes includes trait-mediated effects on nutrient cycling, bioturbation, plant growth, seed dispersal, other dung-based organisms and parasite transmission, as well as some cases of pollination and predation. We identify 66 dung beetle traits that are either response or effect traits, or both, pertaining to six main categories: morphology, feeding, reproduction, physiology, activity and movement. Several traits pertain to more than one category, in particular dung relocation behaviour during nesting or feeding. We also identify 136 trait-response and 77 trait-effect relationships in dung beetles. No response to environmental stressors nor effect over ecological processes were related with traits of a single category. This highlights the interrelationship between the traits shaping body-plans, the multi-functionality of traits, and their role linking responses to the environment and effects on the ecosystem. Despite current developments in dung beetle functional ecology, many knowledge gaps remain, and there are biases towards certain traits, functions, taxonomic groups and regions. Our framework provides the foundations for the thorough development of trait-based dung beetle ecology. It also serves as an example framework for other taxa.

Emission estimates and air quality simulation on Lombardy during lockdown.

This paper illustrates the study carried out by ARPA Lombardia to quantify the variation in daily emissions of the main pollutants and their impacts on air quality in Lombardy during the anti-COVID-19 lockdown between the end of February and the end of May 2020. A methodology for emission estimates was developed over Lombardy for this purpose and later was extended to larger areas: the Po-basin, (LIFE PREPAIR 2020) and the entire Italy (PULVIRUS 2021). In this study, the daily emissions estimates were derived by combining data from air emission inventory of Lombardy and a set of indicators that allowed to update the estimates and describe the temporal and spatial variations of the emission sources. The calculation of emission variation was conducted for all the main pollutants (PM10, NH3, NOx, SO2, NMVOC) and the greenhouse gases; then, the impact on air quality concentrations was simulated by the chemical and transport model FARM, that also allows to track secondary particulate and its variability in time and space on the basis of nonlinear processes and weather conditions. The estimated emission reduction, compared to the expected average value in the absence of anti-COVID-19 measures, daily varies depending on pollutants and is mainly affected by reductions in road traffic emissions and an estimated increase in domestic heating emissions. Simulations confirm strong reductions of NO2 atmospheric average concentrations, slightly variations of PM10 averages and a potential growth of tropospheric ozone.

Low resource availability drives feeding niche partitioning between wild bees and honeybees in a European city.

Cities are socioecological systems that filter and select species, therefore establishing unique species assemblages and biotic interactions. Urban ecosystems can host richer wild bee communities than highly intensified agricultural areas, specifically in resource-rich urban green spaces such as allotments and family gardens. At the same time, urban beekeeping has boomed in many European cities, raising concerns that the fast addition of a large number of managed bees could deplete the existing floral resources, triggering competition between wild bees and honeybees. Here, we studied the interplay between resource availability and the number of honeybees at local and landscape scales and how this relationship influences wild bee diversity. We collected wild bees and honeybees in a pollination experiment using four standardized plant species with distinct floral morphologies. We performed the experiment in 23 urban gardens in the city of Zurich (Switzerland), distributed along gradients of urban and local management intensity, and measured functional traits related to resource use. At each site, we quantified the feeding niche partitioning (calculated as the average distance in the multidimensional trait space) between the wild bee community and the honeybee population. Using multilevel structural equation models (SEM), we tested direct and indirect effects of resource availability, urban beekeeping, and wild bees on the community feeding niche partitioning. We found an increase in feeding niche partitioning with increasing wild bee species richness. Moreover, feeding niche partitioning tended to increase in experimental sites with lower resource availability at the landscape scale, which had lower abundances of honeybees. However, beekeeping intensity at the local and landscape scales did not directly influence community feeding niche partitioning or wild bee species richness. In addition, wild bee species richness was positively influenced by local resource availability, whereas local honeybee abundance was positively affected by landscape resource availability. Overall, these results suggest that direct competition for resources was not a main driver of the wild bee community. Due to the key role of resource availability in maintaining a diverse bee community, our study encourages cities to monitor floral resources to better manage urban beekeeping and help support urban pollinators.

Different roles of concurring climate and regional land-use changes in past 40 years' insect trends.

Climate and land-use changes are main drivers of insect declines, but their combined effects have not yet been quantified over large spatiotemporal scales. We analysed changes in the distribution (mean occupancy of squares) of 390 insect species (butterflies, grasshoppers, dragonflies), using 1.45 million records from across bioclimatic gradients of Switzerland between 1980 and 2020. We found no overall decline, but strong increases and decreases in the distributions of different species. For species that showed strongest increases (25% quantile), the average proportion of occupied squares increased in 40 years by 0.128 (95% credible interval: 0.123-0.132), which equals an average increase in mean occupancy of 71.3% (95% CI: 67.4-75.1%) relative to their 40-year mean occupancy. For species that showed strongest declines (25% quantile), the average proportion decreased by 0.0660 (95% CI: 0.0613-0.0709), equalling an average decrease in mean occupancy of 58.3% (95% CI: 52.2-64.4%). Decreases were strongest for narrow-ranged, specialised, and cold-adapted species. Short-term distribution changes were associated to both climate changes and regional land-use changes. Moreover, interactive effects between climate and regional land-use changes confirm that the various drivers of global change can have even greater impacts on biodiversity in combination than alone. In contrast, 40-year distribution changes were not clearly related to regional land-use changes, potentially reflecting mixed changes in local land use after 1980. Climate warming however was strongly linked to 40-year changes, indicating its key role in driving insect trends of temperate regions in recent decades.

Quantification of Carbonic Anhydrase Inhibitors and Metabolites in Urine and Hair of Patients and Their Relatives.

Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 µL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2-501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9-125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL-0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4-79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7-437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1-0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06-0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13-1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair.