Conservation of pollinators in traditional agricultural landscapes – New challenges in Transylvania (Romania) posed by EU accession and recommendations for future research

Farmland biodiversity is strongly declining in most of Western Europe, but still survives in traditional low intensity agricultural landscapes in Central and Eastern Europe. Accession to the EU however intensifies agriculture, which leads to the vanishing of traditional farming. Our aim was to describe the pollinator assemblages of the last remnants of these landscapes, thus set the baseline of sustainable farming for pollination, and to highlight potential measures of conservation. In these traditional farmlands in the Transylvanian Basin, Romania (EU accession in 2007), we studied the major pollinator groups-wild bees, hoverflies and butterflies. Landscape scale effects of semi-natural habitats, land cover diversity, the effects of heterogeneity and woody vegetation cover and on-site flower resources were tested on pollinator communities in traditionally managed arable fields and grasslands. Our results showed: (i) semi-natural habitats at the landscape scale have a positive effect on most pollinators, especially in the case of low heterogeneity of the direct vicinity of the studied sites; (ii) both arable fields and grasslands hold abundant flower resources, thus both land use types are important in sustaining pollinator communities; (iii) thus, pollinator conservation can rely even on arable fields under traditional management regime. This has an indirect message that the tiny flower margins around large intensive fields in west Europe can be insufficient conservation measures to restore pollinator communities at the landscape scale, as this is still far the baseline of necessary flower resources. This hypothesis needs further study, which includes more traditional landscapes providing baseline, and exploration of other factors behind the lower than baseline level biodiversity values of fields under agri-environmental schemes (AES)

Hydration and glycogen affect T1 relaxation times of liver tissue

T1 mapping is a useful tool for the assessment of patients with nonalcoholic fatty liver disease but still suffers from a large unexplained variance in healthy subjects. This study aims to characterize the potential effects of liver glycogen concentration and body hydration status on liver shortened modified Look-Locker inversion recovery (shMOLLI) T1 measurements. Eleven glycogen phantoms and 12 healthy volunteers (mean age: 31 years, three females) were scanned at 3 T using inversion recovery spin echo, multiple contrast spin echo (in phantoms), shMOLLI T1 mapping, multiple-echo spoiled gradient recalled echo and 13C spectroscopy (in healthy volunteers). Phantom r1 and r2 relaxivities were determined from measured T1 and T2 values. Participants underwent a series of five metabolic experiments to vary their glycogen concentration and hydration levels: feeding, food fasting, exercising, underhydration, and rehydration. Descriptive statistics were calculated for shMOLLI T1, inferior vena cava to aorta cross-sectional area ratio (IVC/Ao) as a marker of body hydration status, glycogen concentration, T2* and proton density fat fraction values. A linear mixed model for shMOLLI R1 was constructed to determine the effects of glycogen concentration and IVC/Ao ratio. The mean shMOLLI T1 after fasting was 737 ± 67 ms. The mean within-subject change was 80 ± 45 ms. The linear mixed model revealed a glycogen r1 relaxivity in volunteers (0.18 M−1 s−1, p = 0.03) close to that determined in phantoms (0.28 M−1 s−1). A unit change in IVC/Ao ratio was associated with a drop of −0.113 s−1 in R1 (p < 0.001). This study demonstrated a dependence of liver shMOLLI T1 values on liver glycogen concentration and overall body hydration status. Interparticipant variation of hydration status should be minimized in future liver MRI studies. Additionally, caution is advised when interpreting liver T1 measurements in participants with excess liver glycogen

Water‐suppression cycling 3‐T cardiac 1H‐MRS detects altered creatine and choline in patients with aortic or mitral stenosis

Cardiac proton spectroscopy (1H‐MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water‐suppression cycling (WSC) to two single‐voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard &lsquo;WET&rsquo; water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3&thinsp;&plusmn;&thinsp;4.0 years; body mass index [BMI] 23.7&thinsp;&plusmn;&thinsp;4.1 kg/m2). Fat fraction, creatine concentration and choline concentration when quantified by STEAM‐WET were 0.30%&thinsp;&plusmn;&thinsp;0.11%, 29.6&thinsp;&plusmn;&thinsp;7.0 &mu;mol/g and 7.9&thinsp;&plusmn;&thinsp;6.7 &mu;mol/g, respectively; and when quantified by PRESS‐WSC they were 0.30%&thinsp;&plusmn;&thinsp;0.15%, 31.5&thinsp;&plusmn;&thinsp;3.1 &mu;mol/g and 8.3&thinsp;&plusmn;&thinsp;4.4 &mu;mol/g, respectively. Compared with STEAM‐WET, PRESS‐WSC gave spectra whose fitting quality expressed by Cram&eacute;r‐Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM‐WET and PRESS‐WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9&thinsp;&plusmn;&thinsp;6.3 years; BMI 27.4&thinsp;&plusmn;&thinsp;4.3 kg/m2). Spectra were of analysable quality in eight patients for STEAM‐WET, and in nine for PRESS‐WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS‐WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM‐WET for detecting altered creatine and choline concentrations in patients with valve disease.</p

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

Background The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. Methods Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. Findings At 2–3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). Interpretation A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. Funding NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis

Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63–68) and 86% (84–87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37–39) and specificity of 90% (89–91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies

The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV Positive Patients and for Detecting Disease Progression.

In the era of primary vaccination against HPV and at the beginning of the low prevalence of cervical lesions, introduction of screening methods that can distinguish between low- and high-grade lesions is necessary in order to maintain the positive predictive value of screening. This case-control study included 562 women who attended cervical screening or were referred for colposcopy and 140 disease free controls, confirmed by histology and/or cytology. The cases were stratified by age. Using routine exfoliated liquid based cytological samples RT-PCR measurements of biomarker genes, high-risk HPV testing and liquid based cytology were performed and used to evaluate different testing protocols including sets of genes/tests with different test cut-offs for the diagnostic panels. Three new panels of cellular biomarkers for improved triage of hrHPV positive women (diagnostic panel) and for prognostic assessment of CIN lesions were proposed. The diagnostic panel (PIK3AP1, TP63 and DSG3) has the potential to distinguish cytologically normal hrHPV+ women from hrHPV+ women with CIN2+. The prognostic gene panels (KRT78, MUC5AC, BPIFB1 and CXCL13, TP63, DSG3) have the ability to differentiate hrHPV+ CIN1 and carcinoma cases. The diagnostic triage panel showed good likelihood ratios for all age groups. The panel showed age-unrelated performance and even better diagnostic value under age 30, a unique feature among the established cervical triage tests. The prognostic gene-panels demonstrated good discriminatory power and oncogenic, anti-oncogenic grouping of genes. The study highlights the potential for the gene expression panels to be used for diagnostic triage and lesion prognostics in cervical cancer screening