Porto-sinusoidal vascular disorder and nephrotic-range proteinuria due to venous vasculitis in Behçet's disease.

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD.

Differential effects and success stories of distance education in Covid-19 lockdowns on the development of reading comprehension in primary schools.

In the current study, the development in reading comprehension performance of students in lower-SES versus higher-SES schools during and after school closures due to Covid-19 lockdowns was examined, and compared to a normed reference group. Furthermore, we explored protective factors against negative effects at the time of school closures, by pinpointing successful practices in a sub sample of resilient lower-SES schools. The total sample consisted of 2202 students followed from grade 2-4. Overall, we found that students in lower-SES schools made less progress over time than students in higher-SES schools. On average, students made less progress during the lockdowns, but here, the interaction with SES was not significant. Students' reading comprehension levels partially recovered after the lockdowns. Questionnaire-data revealed that schools were better prepared during the second lockdown, with teachers making more use of digital means, and providing more online reading instruction. In addition, collaboration with the parents seemed to have improved. The in depth interviews with resilient lower-SES schools revealed that the introduction of online education and investing in educational partnerships with parents may have helped to minimize the negative impact of lockdowns. We conclude that lockdowns have a negative effect on the development of reading education, but that students are resilient. Digital means and partnership with parents may be seen as protective factors to attenuate the negative effects of emergency remote teaching.

Diagnostic accuracy of calretinin and acetylcholinesterase staining of rectal suction biopsies in Hirschsprung disease examined by unexperienced pathologists.

Rectal suction biopsy (RSB) is a gold standard for diagnosing Hirschsprung disease (HD). Calretinin staining of RSB is increasingly used by experienced pathologists due to non-complex examination and comparable diagnostic accuracy with acetylcholinesterase (AChE). However, the diagnostic accuracy of calretinin examined by unexperienced pathologists remains to be elucidated. Therefore, we aim to compare diagnostic accuracy of calretinin with AChE on RSB for diagnosing HD when examined by unexperienced pathologists. We prospectively analyzed sections from RSB stained with AChE + HE and calretinin. Blinded examination was done by five unexperienced pathologists (pathology residents) and three experienced pathologists (senior pediatric gastro-enterology pathologists) assessing for the presence of HD. Cases for the study included ones proven to be HD on resection specimens and cases without HD. Diagnostic accuracy was determined calculating area under the curve (AUC), sensitivity, specificity, likelihood ratio, and posttest probability. Fleiss' kappa analysis was performed to assess interobserver agreement between reviewers. Eleven of 18 included patients (61%) were diagnosed with HD. Comparing the diagnostic accuracy of unexperienced pathologists, calretinin versus AChE + HE showed sensitivity of 80.0% versus 74.5% and specificity of 100% versus 65.4%, AUC of 0.87 (0.78-0.96) versus 0.59 (0.45-0.72). Unexperienced pathologists showed substantial agreement with calretinin (kappa 0.72 [0.61-0.84]) and fair agreement with AChE + HE (kappa 0.34 [0.23-0.44]). We found calretinin having higher diagnostic accuracy in diagnosing HD compared to AChE + HE when examined by unexperienced pathologists. Therefore, we recommend to use calretinin as the standard technique for staining RSB in diagnosing HD.

Estimating ankle torque and dynamics of the stabilizing mechanism: No need for horizontal ground reaction forces.

Changes in human balance control can objectively be assessed using system identification techniques in combination with support surface translations. However, large, expensive and complex motion platforms are required, which are not suitable for the clinic. A treadmill could be a simple alternative to apply support surface translations. In this paper we first validated the estimation of the joint stiffness of an inverted pendulum using system identification methods in combination with support surface translations, by comparison with the joint stiffness calculated using a linear regression method. Second, we used the system identification method to investigate the effect of horizontal ground reaction forces on the estimation of the ankle torque and the dynamics of the stabilizing mechanism of 12 healthy participants. Ankle torque and resulting frequency response functions, which describes the dynamics of the stabilizing mechanism, were calculated by both including and excluding horizontal ground reaction forces. Results showed that the joint stiffness of an inverted pendulum estimated using system identification is comparable to the joint stiffness estimated by a regression method. Secondly, within the induced body sway angles, the ankle torque and frequency response function of the joint dynamics calculated by both including and excluding horizontal ground reaction forces are similar. Therefore, the horizontal ground reaction forces play a minor role in calculating the ankle torque and frequency response function of the dynamics of the stabilizing mechanism and can thus be omitted.

Radial oxygen loss by the cushion plant Eriocaulon schimperi prevents methane emissions from an East-African mountain mire.

Groundwater-fed fens are known sources of methane (CH4 ) emissions to the atmosphere, and these are known to be mediated by the vegetation. In a fen located in the Bale Mountains, Ethiopia, we assessed the effects of a cushion plant (Eriocaulon schimperi) and a sedge (Carex monostachya) on rhizosphere biogeochemistry. Methane and CO2 concentrations and pH were measured in pore-water at different depths in the profile. Redox potentials and NaCl-extractable element concentrations were analysed in soil samples from sites dominated by either E. schimperii or C. monostachya. Nutrient and element concentration were analysed in plant tissues. At Carex-dominated sites, CH4 concentrations increased from 70 µmol·l-1 at a depth of 10 cm to 130 µmol·l-1 at a depth of 100 cm. CH4 concentrations at Eriocaulon-dominated sites were almost zero (<1 µmol·l-1 ) to a depth of 100 cm. Simultaneously, soil redox potentials and CO2 concentrations were higher at Eriocaulon-dominated sites, indicating a low potential for CH4 production and a high potential for CH4 oxidation. Eriocaulon schimperi displayed a root investment strategy to cope with the harsh environment, similar to the cushion plant Astelia pumila in Patagonian bogs. This strategy is characterised by high root/shoot ratios, high root porosity and density under high redox conditions. Both cushion plant species create an aerobic rhizosphere through radial oxygen loss from deep roots, which strongly reduce CH4 fluxes to the atmosphere.

The effect of housing condition on the performance of two types of activity meters to detect estrus in dairy cows.

When the daily routine of a cow is disturbed, it may have a detrimental effect on the performance of activity meters to detect estrus. It is possible that during the pasture period, the daily routine of cows is disturbed, adversely affecting the performance of activity meters to detect estrus which does not happen when the cows are housed indoors. The objective of this study was to investigate whether housing conditions (pasture or indoor) affected the performance of activity meters to detect estrus in dairy cows. In this research, two types of activity meters were used, an activity meter attached to the leg and one mounted on the neck. Cows of two different herds were equipped with the Smarttag Leg and the Smarttag Neck (Nedap livestock management, Groenlo, the Netherlands). The study began during the pasture period (September) and ended during the indoor period (January). The pasture period ended at the beginning of November. So, about two months of pasture period and two months of indoor period were studied. Milk samples were collected twice a week during the morning milking and true estrus was determined by milk progesterone concentrations. In total, the dataset consisted of 95 true estrous periods and 1992 true non-estrous days of 56 cows for the pasture period and 138 true estrous periods and 3164 true non-estrous days of 65 cows for the indoor period. Overall, no differences in sensitivity, positive predictive value (PPV) and specificity were found between the pasture and indoor period for both types of sensors. There was also no difference in the performance between leg and neck activity meters. Sensitivity was between 76 and 82%, PPV was between 87 and 92% and specificity was between 99 and 100%. In conclusion, the sensitivity, PPV and specificity did not differ between the pasture and indoor period. This means that, in our study, the performance of both types of activity meters to detect estrus is not affected by housing conditions.

Thrombin contributes to protective immunity in pneumonia-derived sepsis via fibrin polymerization and platelet-neutrophil interactions.

Essentials Immunity and coagulation are linked during sepsis but the role of thrombin is not fully elucidated. We investigated the effect of thrombin inhibition on murine Klebsiella pneumosepsis outcome. Thrombin is crucial for survival and limiting bacterial growth in pneumonia derived sepsis. Thrombin improves host defense via fibrin and enhancement of platelet-neutrophil interactions. SUMMARY: Background Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental to the outcome because of microvascular failure but can also enhance host defense. The role of thrombin therein has not been fully elucidated. Objective We aimed to investigate the contribution of thrombin to the host response during pneumonia-derived sepsis. Methods Mice treated with the specific thrombin inhibitor dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K.) pneumoniae via the airways. In subsequent infection experiments, mice were additionally treated with ancrod to deplete fibrinogen. Ex vivo Klebsiella growth was assessed by incubating human whole blood or specific blood components in various conditions with Klebsiella. Results Thrombin inhibition by dabigatran enhanced bacterial outgrowth and spreading, and accelerated mortality. Thrombin inhibition did not influence neutrophil recruitment to the lung or activation or neutrophil extracellular trap formation. Dabigatran reduced D-dimer formation and fibrin deposition in the lung. Fibrin depletion also enhanced bacterial outgrowth and spreading, and thrombin inhibition had no additional effect. Both thrombin and fibrin polymerization inhibited ex vivo Klebsiella outgrowth in human whole blood, which was neutrophil dependent, and the effect of thrombin required the presence of platelets and platelet protease activated receptor-1. In vivo thrombin inhibition reduced platelet-neutrophil complex formation and endothelial cell activation, but did not prevent sepsis-induced thrombocytopenia or organ damage. Conclusions These results suggest that thrombin plays an important role in protective immunity during pneumonia-derived sepsis by fibrin polymerization and enhancement of platelet-neutrophil interactions.

General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation.

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.

Susceptibility to acidification of groundwater-dependent wetlands affected by water level declines, and potential risk to an early-breeding amphibian species.

Eggs of the Western spadefoot toad (Pelobates cultripes) reached a 100% mortality in all 29 clutches deposited at a pH below 5.0 in a temporary pond of the Doñana National Park (SW Spain) throughout the wet season of 2006-2007. A similar trend was detected in a neighbouring pond. The proximity of these two ponds to a groundwater pumping area (<1.5km), prompted us to elucidate the possible links between the reduction in pond hydroperiod over past decades (1989-2008) and the decrease of groundwater pH-buffering capacity. The average hydroperiod had decreased by 4months since 1998-99 in the pond where the extensive egg mortality had occurred. The total alkalinity, and the Mg(2+)concentration had also significantly declined in the shallow water-table since 1998-99, from an average of 8.56 to 0.32meql(-1), and of 3.57 to 1.15meql(-1), respectively. This decline of the shallow groundwater buffering capacity could turn this pond more susceptible to the inorganic acidity associated with pyrite oxidation as the sediment S content was often above 0.03%. The initial ratio of S/Ca+Mg in the summer dry sediment was a good predictor of pore-water pH on re-wetting after desiccation (r(2)=0.802, p<0.01). Therefore, this ratio can give some anticipation to mitigate the impact of acidity on toad hatching before these temporary ponds are reflooded on the next wet season. Our results suggest that the long-term damage to pond water levels can trigger a potential risk of soil acidification in the presence of iron-sulphide minerals.

Renal endothelial protein C receptor expression and shedding during diabetic nephropathy.

UNLABELLED: Essentials Endothelial protein C receptor (EPCR) promotes diabetic nephropathy (DN) outcome improvement. Renal expression and shedding of EPCR were measured in diabetic patients with or without DN. Inhibition of metalloproteinase-driven EPCR shedding restored glomerular endothelium phenotype. EPCR shedding through metalloproteinase ADAM17 contributes to the worsening of DN. SUMMARY: Background Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. The endothelial protein C receptor (EPCR) and its ligand (activated protein C) have been shown to ameliorate the phenotype of DN in mice. EPCR activity can be regulated by proteolytic cleavage involving ADAMs, yielding a soluble form of EPCR (sEPCR). Objective To characterize the renal expression and shedding of EPCR during DN. Methods EPCR levels were measured in plasma, urine and biopsy samples of diabetic patients with (n = 73) or without (n = 63) DN. ADAM-induced cleavage of EPCR was investigated in vitro with a human glomerular endothelium cell line. Results DN patients showed higher plasma and urinary levels of sEPCR than diabetic controls (112.2 versus 135.2 ng mL(-1) and 94.35 versus 140.6 ng mL(-1) , respectively). Accordingly, glomerular endothelial EPCR expression was markedly reduced in patients with DN, and this was associated with increased glomerular expression of ADAM-17 and ADAM-10. In vitro, EPCR shedding was induced by incubation of glomerular endothelium in high-glucose medium, and this shedding was suppressed by ADAM-17 inhibition or silencing, which led to improved vascular endothelial cadherin (VE-cadherin) expression and reduced mRNA expression of transforming growth factor (TGF)-ß. In addition, EPCR silencing led to minor effects on VE-cadherin but to a significant increase in TGF-ß mRNA expression. Conclusion Inhibition of ADAM-driven glomerular EPCR shedding restored the endothelial phenotype of glomerular endothelium, whereas EPCR silencing led to enhanced expression of TGF-ß, a marker of endothelial-mesenchymal transition. These findings demonstrate that EPCR shedding driven by ADAMs contributes to the worsening of DN.