Fine tuning of crystal architecture by intermolecular interactions: synthon engineering

There has been a long time effort to influence or favourably fine tune structural properties by introduction of substituents or guest molecules of different sizes, shapes and chemical composition to consequently alter physico-chemical properties of the respective crystals. These attempts require the recognition, understanding and application of intermolecular interactions, crystallographic and, in case of occurrence, non-crystallographic symmetries. It brings us to the field of crystal engineering, which aims to produce new substances with required properties based on the knowledge of the structural properties of already characterised solids. A series of calixarene crystal structures are presented where the crystal packing is determined by spatial or by electrostatic effects. A series of laterally substituted calixarenes where both steric requirements and electrostatic forces play a role in the crystal architecture shows how the supramolecular synthon can be engineered

N-acetyl-b-D-glucosaminidase: A potential cardiorenal biomarker with a relevant impact on ICD shock therapies and mortality

Aims Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown. Methods We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months). Results KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1:r= .34,P < .001; NAG:r= .47,P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P= .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (eachP < .001). Elevated KIM-1 showed no significant differences (eachP= n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (eachP < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (eachP= n.s.). Conclusion Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies

Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19

Introduction: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. Methods: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. Results: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28–11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13–6.28] per SD). Conclusion: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34–24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30–17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients

The Role of Information and Financial Reporting in Corporate Governance and Debt Contracting

We review recent literature on the role of financial reporting transparency in reducing governance-related agency conflicts among managers, directors, and shareholders, as well as in reducing agency conflicts between shareholders and creditors, and offer researchers some suggested avenues for future research. Key themes include the endogenous nature of debt contracts and governance mechanisms with respect to information asymmetry between contracting parties, the heterogeneous nature of the informational demands of contracting parties, and the heterogeneous nature of the resulting governance and debt contracts. We also emphasize the role of a commitment to financial reporting transparency in facilitating informal multiperiod contracts among managers, directors, shareholders, and creditors

NAG: potential cardiorenal biomarker indicates the progression of chronic kidney disease in implantable cardioverter defibrillator patients, contrary to KIM-1

Aim: NAG and KIM-1 as markers of tubular damage are suggested as potential biomarkers for the cardiorenal syndrome. Aim of the study was to assess the prognostic capability of NAG and KIM-1 regarding progression of chronic kidney disease (CKD) in patients with implantable cardioverter defibrillator (ICD). Materials & methods: We included 313 patients with an ICD and collected plasma and urine samples. Follow-up was performed after 51 months (interquartile range [IQR]: 25-55). Outcome of interest was continuous CKD progression defined as persistent decline in estimated glomerular filtration rate category accompanied by a >= 25% drop of baseline estimated glomerular filtration rate. Results: Average four (IQR: 2-6) follow-up values of serum creatinine per patient were obtained. During followup 29 patients (9%) developed a continuous CKD progression. NAG was shown as independent predictor for continuous CKD progression (p = 0.01), opposite to KIM-1 (p = n.s.). Conclusion: NAG was shown as predictor for a progressive and real deterioration of kidney function in patients with ICD

Intestinal IgA positive plasma cells are highly sensitive indicators of alloreaction early after allogeneic transplantation and associate with both, graft-<i>versus-</i>host disease and relapse related mortality

Intestinal IgA is strongly involved in microbiota homeostasis. Since microbiota disruption is a major risk factor of acute GvHD, we addressed the kinetics of intestinal IgA-positive (IgA+) plasma cells by immunohistology in a series of 430 intestinal biopsies obtained at a median of 1,5 months after allogeneic stem cell transplantation from 115 patients (pts) at our center. IgA+ plasma cells were located in the subepithelial lamina propria and suppressed in the presence of histological aGvHD (GvHD lerner stage 0: 131+/- 8 IgA+ plasma cells/mm2; stage 1-2: 108 +/-8 IgA+ plasma cells/ mm2; stage 3-4: 89+/-16 IgA+ plasma cells/ mm2, p 0.004). Overall, pts with IgA+ plasma cells below median had an increased treatment related mortality (p = 0.04). Time courses suggested a gradual recovery of IgA+ plasma cells after day 100 in the absence but not in the presence of GvHD. Vice versa IgA+ plasma cells above median early after SCT were predictive of relapse and relapse related mortality (RRM): Pts with low IgA+ cells had a 15% RRM at 2 and at 5 yrs, while pts with high IgA+ cells had a 31% RRM at 2 years and more than 46% at 5 years; multivariate analysis indicated high IgA+ plasma cells in biopsies (HR 2.7 (95% CI 1.04-7.00) as independent predictors of RRM, whereas Lerner stage and disease stage themselves did not affect RRM. In contrast, IgA serum levels at the time of biopsy were not predictive for RRM. In summary, our data indicate that IgA+ cells are highly sensitive indicators of alloreaction early after allo-SCT showing association with TRM but also allowing prediction of relapse independently from the presence of overt GvHD