[Quantification of Ki-67 in PitNET (pituitary neuroendocrine tumors)/adenomas]. / Quantifizierung von Ki-67 in PitNET ("pituitary neuroendocrine tumors")/Adenomen.

This study is the first to compare the determination of the Ki-67 index in pituitary neuroendocrine tumors (PitNET)/pituitary adenomas by pathologists with a computerized method (Cognition MasterSuite from VMScope, Berlin, Germany). PitNET/pituitary adenomas often show a low proliferation index. Observer variability is high, especially when estimating in this low percentage range. A more reliable determination would be possible using the four-eyes principle, but this cannot be realized continuously; thus, digital image analysis is a promising solution. In the study, there was clear agreement between the Ki-67 estimate by two experienced pathologists and the determination with the aid of digital image analysis. The digital image analysis system is excellent for determining the proliferation rate of PitNET/pituitary adenomas and can therefore be used to determine the "third" and "fourth eye".

Indications for the Postpartum Oral Glucose Tolerance Test.

BACKGROUND: Gestational diabetes mellitus (GDM) affects more than 50 000 pregnant women in Germany every year. In postpartum diabetes screening, a 75 g oral glucose tolerance test (OGT) is recommended. This is time-consuming and can have side effects, and only 40% of mothers take it. The determination of pre-test probabilities might obviate the need for OGT except in women who are at particular risk. METHODS: We analyzed 5444 cases of GDM from the GestDiab registry over the period 2015-2019. The pretest probabilities of a postpartum diagnosis of diabetes mellitus (DM) or prediabetes were calculated on the basis of clinical variables including postpartum venous fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). RESULTS: In 0.77% of mothers with a history of GDM in whom DM was not detected by FPG or HbA1c, postpartum DM was diagnosed on the basis of the 2-hour value in the OGT. Individual estimation of the pre-test probability of a diagnosis by OGT of postpartum DM or prediabetes was possible with the aid of the FPG and HbA1c values and clinical predictors including insulin treatment during pregnancy, obesity, GDM diagnosed before 24 weeks of gestation, age over 35, and a 1-hour value in the diagnostic OGT during pregnancy of 180 mg/dL (10.0 mmol/L) or above. The pretest probability of postpartum DM in the study group ranged from 0.11% to 4.17%, and that of postpartum prediabetes from 6.4% to 16.3%. CONCLUSION: The probability of a diagnosis of postpartum diabetes by OGT after GDM can be estimated in postpartum screening on the basis of various parameters. This enables risk-adapted counseling of the affected women along with a long-term strategy for diabetes prevention and follow-up. The findings of our study should be verified by further research.

Risk mitigation measures for pesticide runoff: How effective are they?

BACKGROUND: One of the most important sources of pesticide pollution of surface waters is runoff and erosion from agricultural fields after rainfall. This study analyses the efficacy of different risk mitigation measures to reduce pesticide runoff and erosion inputs into surface waters from arable land excluding rice fields. RESULTS: Three groups of risk mitigation measures were quantitatively analyzed: vegetative filter strips, micro-dams in row crops and soil conservation measures. Their effectiveness was evaluated based on a meta-analysis of available experimental data using statistical methods such as classification and regression trees, and exploratory data analysis. Results confirmed the effectiveness of vegetative filter strips and micro-dams. Contrary to common assumption, the width of vegetative filter strips alone is not sufficient to predict their effectiveness. The effectiveness of soil conservation measures (especially mulch-tillage) varied widely. This was in part due to the heterogeneity of the available experimental data, probably resulting from the inconsistent implementation and the inadequate definitions of these measures. CONCLUSION: Both vegetative filter strips and micro-dams are effective and suitable, and can therefore be recommended for quantitative assessment of environmental pesticide exposure in surface waters. However, the processes of infiltration and sedimentation in vegetative filter strips should be simulated with a mechanistic model like Vegetative Filter Strip Modeling System, VFSMOD. The reduction effect of micro-dams can be modelled by reducing the runoff curve number, e.g., in the pesticide root zone model, PRZM. Soil conservation measures are in principle promising, but further well-documented data are needed to determine under which conditions they are effective. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Nanopharmaceuticals (Au-NPs) after use: Experiences with a complex higher tier test design simulating environmental fate and effect.

The current environmental hazard assessment is based on the testing of the pristine substance. However, it cannot be excluded that (nano)pharmaceuticals are excreted into sewage during the use phase followed by entry into wastewater treatment plants (WWTPs). Sorption to sewage sludge or release via effluent can result in modified ecotoxicological effects which possibly can only be detected with a modified test approach. The objective of our study was to investigate a realistic exposure scenario for metallic nanoparticles (NPs) in pharmaceutical products, excreted into effluent, and released into the environment after treatment in WWTPs. The test approach was illustrated by using gold (Au) NPs. Effluent from model WWTPs were investigated in aquatic tests (Daphnia magna, fish cell lines). Sewage sludge was used as a sole food source (Eisenia fetida) or mixed with soil and used as test medium (soil microorganisms, Folsomia candida, Enchytraeus crypticus). To cover the aspect of regulation, the test systems described in OECD-test guidelines (OECD TG 201, 211, 220, 232, 249, 317) were applied. Modifications and additional test approaches were included to meet the needs arising out of the testing of nanomaterials and of the exposure scenarios. The results were assessed regarding the suitability of the test design and the toxicity of Au-NPs. Except for activated sludge as a sole food source for E.fetida, the selected test approach is suitable for the testing of nanomaterials. Additional information can be gained when compared to the common testing of the pristine nanomaterials in the standardized test systems. Effects of Au-NPs were observed in concentrations exceeding the modeled environmental.

Impact of anthropogenic activities on water quality and plankton communities in the Day River (Red River Delta, Vietnam).

Planktons are a major component of food web structure in aquatic ecosystems. Their distribution and community structure are driven by the combination and interactions between physical, chemical, and biological factors within the environment. In the present study, water quality and the community structure of phytoplankton and zooplankton were monthly investigated from January to December 2015 at 11 sampling sites along the gradient course of the Day River (Red River Delta, northern Vietnam). The study demonstrated that the Day River was eutrophic with the average values of total phosphorus concentration 0.17 mg/L, total nitrogen concentration 1.98 mg/L, and Chl a 54 µg/L. Microscopic plankton analysis showed that phytoplankton comprised 87 species belonging to seven groups in which Chlorophyceae, Bacillariophyceae, and Cyanobacteria accounted for the most important constituents of the river's phytoplankton assemblage. A total 53 zooplankton species belonging to three main groups including Copepoda, Cladocera, and Rotatoria were identified. Plankton biomass values were greatest in rainy season (3002.10-3 cell/L for phytoplankton and 12.573 individuals/m3 for zooplankton). Using principal correspondence and Pearson correlation analyses, it was found that the Day River was divided into three main site groups based on water quality and characteristics of plankton community. Temperature and nutrients (total phosphorus and total nitrogen) are key factors regulating plankton abundance and distribution in the Day River.

Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile.

PURPOSE: The aim of the study was to evaluate the potential influence of ranibizumab and bevacizumab on platelet activation and aggregation, which are critical processes in the pathogenesis of arterial thromboembolic events (ATEs). METHODS: For the assessment of platelet function, flow cytometry and aggregometry were employed. Platelets were isolated from healthy volunteers and exposed to ranibizumab (1 mg/ml and 150 ng/ml) and bevacizumab (2.5 mg/ml and 3 µg/ml) or their solvents for 10 and 30 min prior to the addition of TRAP (25 µM), PAR-4-AP (25 µM) or thrombin (0.02 U/ml). The surface expression of activated GP IIb/IIIa, P-selectin (CD62P) and platelet-bound stromal cell-derived factor-1 (SDF-1) was measured on resting (nonactivated) and activated platelets by flow cytometry. The platelet aggregation capacity was examined using light transmission aggregometry. RESULTS: The expression of surface activation markers did not differ significantly between nonstimulated and TRAP-, PAR-4-AP- or thrombin-activated platelets after incubating with ranibizumab. However, GP IIb/IIIa, CD62P and SDF-1 were significantly downregulated in PAR-4-AP- and thrombin-activated platelets after exposure to bevacizumab 2.5 mg/ml. In addition, ranibizumab- and bevacizumab-FITC were significantly increased in all activated platelets. No significant differences were observed in the aggregation of activated platelets after incubation with ranibizumab or bevacizumab. CONCLUSION: All ranibizumab concentrations as well as the bevacizumab concentration of 3 µg/ml had no influence on platelet activation and aggregation. Therefore, this in vitro study did not show any relationship between the exposition of activated platelets to ranibizumab or bevacizumab and the development of ATEs. However, the highest level of bevacizumab interfered with platelet activation, leading to downregulation of platelet activation markers. This observation might explain why the systemic treatment with high-dose bevacizumab could be associated with an increased risk of bleeding. Regarding the use of lower intravitreal dosages, further research should focus on the complex interactions between platelets and other cells, such as endothelial cells, which might stronger relate to a potentially increased risk of ATEs and depend on systemic vascular endothelial growth factor levels. Facing the different activation profiles, the diverse effects of the drugs on the cellular level have to be critically scrutinized for their clinical relevance.

Urban structures provide new insights into interactions among grazers and habitat.

A major challenge in ecology is to understand and predict consequences of environmental changes to biological assemblages. Urbanization and associated alteration and destruction of habitat cause profound changes in local biodiversity and the ecology of and interactions among organisms. This study tested hypotheses about interactions among intertidal species on urbanized shores to examine predictions from their known ecology. On natural shores, grazing limpets, Cellana tramoserica, outcompete the smaller limpets, Patelloida latistrigata. The latter shelter among barnacles. On seawalls in Sydney Harbour (Australia), P. latistrigata were found among and on oysters. C. tramoserica were found directly on walls where there were no oysters. To explain these observations, several models were proposed and tested by manipulative experiments in the field: (1) oysters provide habitat for P. latistrigata; (2) negative interactions with C. tramoserica cause P. latistrigata to move on and among oysters; and (3) in areas with oysters, space available for grazing is insufficient for C. tramoserica to survive well. The results showed that C. tramoserica had a negative impact on the survival of P. latistrigata, although not causing the latter to move onto oysters. The oysters directly and indirectly affected P. latistrigata. First, oysters provided habitat and increased survival of P. latistrigata. Second, oysters influenced the interaction between C. tramoserica and P. latistrigata. This "interaction modification" diminished the negative impact of C. tramoserica. The material used to construct a wall did not directly influence the distribution of the limpets. Maintaining oysters on seawalls is, however, important because of their direct and indirect effects on P. latistrigata. It was possible to predict some processes on urbanized shores from known ecology. Other processes could not be predicted, making it necessary to do experiments to understand how built structures influence biological assemblages. This research contributes to understanding how to conserve biodiversity in urban areas.

Differences in male breast cancer stage, tumor size at diagnosis, and survival rate between metropolitan and nonmetropolitan regions.

Although the incidence for breast cancer in men is lower than for women, male breast cancer (MBC) patients are diagnosed at a later stage and have a higher mortality rate than women. This study examined male cases reported from 1988 through 2006 in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for differences in cancer stage, tumor size at diagnosis, and survival rate between metropolitan and nonmetropolitan regions. Pearson's chi-square was used to evaluate differences in stage and tumor size at diagnosis. Cox proportional hazards regression was used to assess survival differences after adjusting for confounders (race, marital status, median family income, age, and education). Regional differences in tumor grade size and stage at diagnosis were not statistically significant; however, survival differences were observed between metropolitan and nonmetropolitan regions. An interaction between nonmetropolitan area and regional stage MBC was a significant predictor of poorer survival. Raising awareness of MBC in nonmetropolitan areas could save the lives of many men and action should be taken to improve health care access, treatment, and thus prognosis in this population.

The Caulerpa racemosa invasion: a critical review.

Caulerpa racemosa var. cylindracea is a marine Chlorophyta introduced into the Mediterranean Sea from south-western Australia. Since 1990, it has been invading the Mediterranean Sea and the Canary Islands, raising ecological problems. Although this invasion event can be considered as one of the most serious in the history of species introduced into the Mediterranean Sea, C. racemosa has not triggered as much attention as the famous "killer alga"Caulerpa taxifolia. The aim of the present study was: (i) to summarize the current state of knowledge with regard to the distribution, the various biological and ecological characteristics of the introduced C. racemosa and its impact on the Mediterranean coastal environment; (ii) to discuss the various hypotheses regarding the explanation for its rapid and successful spread; (iii) to investigate the disparity in the treatment of C. racemosa and Caulerpa taxifolia invasions; and (iv) to outline future research needs.

Acute nosocomial HCV infection detected by NAT of a regular blood donor.

BACKGROUND: Routine HCV NAT of blood donors to detect persons in the preseroconversion phase of acute infection was introduced in Canada in October 1999. The source of virus exposure was investigated in the first, and to date only, blood donor found to be HCV NAT positive, anti-HCV negative in Canada. He was a regular donor with none of the commonly reported risk factors for HCV infection. STUDY DESIGN AND METHODS: Epidemiologic follow-up revealed that the blood donor had received antibiotics at an outpatient IV clinic 5 weeks before donation. IV solution bags and tubing for individual patients were stored in the clinic, and then the same equipment was used each time the patient returned for the next dose of antibiotics until it was replaced after every 72-hour period. Among eight other patients whose clinic visitation times overlapped was a man with chronic HCV infection. Genomic sequencing of HCV isolates from the blood donor, the patient with chronic hepatitis C, and local controls was carried out to study possible nosocomial infection. RESULTS: Genomic sequencing showed a high degree of relatedness in the hypervariable region of HCV isolates from the blood donor and putative source patient as compared with controls. Detailed molecular analysis of quasispecies of the HCV isolates further indicated that viruses from the two individuals were genetically very close to each other. CONCLUSION: The introduction of routine screening of blood donors by HCV NAT was directly responsible for the early detection and investigation of an unusual case of HCV infection involving a regular donor. Genomic sequencing studies provided firm evidence of patient-to-patient transmission of HCV in an IV clinic. The report clearly demonstrates the value of molecular fingerprinting in tracking nosocomial HCV infections.