Validation of Fetal Medicine Foundation competing-risks model for small-for-gestational-age neonate in early third trimester.

OBJECTIVE: To evaluate the new 36-week Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at an earlier gestation of 30 + 0 to 34 + 0 weeks. METHODS: This was a retrospective multicenter cohort study of prospectively collected data on 3012 women with a singleton pregnancy undergoing ultrasound examination at 30 + 0 to 34 + 0 weeks' gestation as part of a universal screening program. We used the default FMF competing-risks model for prediction of SGA at 36 weeks' gestation combining maternal factors (age, obstetric and medical history, weight, height, smoking status, race, mode of conception), estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI) to calculate risks for different cut-offs of birth-weight percentile and gestational age at delivery. We examined the accuracy of the model by means of discrimination and calibration. RESULTS: The prediction of SGA < 3rd percentile improved with the addition of UtA-PI and with a shorter examination-to-delivery interval. For a 10% false-positive rate, maternal factors, EFW and UtA-PI predicted 88.0%, 74.4% and 72.8% of SGA < 3rd percentile delivered at < 37, < 40 and < 42 weeks' gestation, respectively. The respective values for SGA < 10th percentile were 86.1%, 69.3% and 66.2%. In terms of population stratification, if the biomarkers used are EFW and UtA-PI and the aim is to detect 90% of SGA < 10th percentile, then 10.8% of the population should be scanned within 2 weeks after the initial assessment, an additional 7.2% (total screen-positive rate (SPR), 18.0%) should be scanned within 2-4 weeks after the initial assessment and an additional 11.7% (total SPR, 29.7%) should be examined within 4-6 weeks after the initial assessment. The new model was well calibrated. CONCLUSIONS: The 36-week FMF competing-risks model for SGA is also applicable and accurate at 30 + 0 to 34 + 0 weeks and provides effective risk stratification, especially for cases leading to delivery < 37 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Giant uterine STUMP in pregnancy: A rare case report with preservation of fertility.

BACKGROUND: Smooth muscle tumors of uncertain malignant potential (STUMPs) are infrequent and represent an extremely rare cause of oligohydramnios in pregnant women. DESCRIPTION OF THE CASE: A 34-year-old woman at 25 weeks of gestation was referred with clinical features indicative of anemia. The transabdominal ultrasound revealed a fetus with appropriate growth for the gestational age, with oligohydramnios and a giant uterine mass. At 30 weeks of gestation, due to anhydramnios and repeated non-reassuring non-stress tests, a cesarean section was performed, followed by a myomectomy of a 9 kg mass. A neonate weighing 1,350 g was delivered (Apgar score 1΄: 4, 5΄: 7). The woman preserved her fertility and had an uneventful recovery during the puerperium, while the final histology revealed multiple STUMPs. The postoperative management included follow-up every six months for five years. CONCLUSION: This is the only reported case of a pregnant woman with STUMPs of this size that underwent myomectomy during the cesarean section and avoided hysterectomy. HIPPOKRATIA 2021, 25 (4):169-171.

Is nuchal translucency measurement feasible in early pregnancy?

BACKGROUND: To investigate whether early nuchal translucency measurement at 7+0 to 9+0 weeks (NT7-9w) is feasible, obtain normal values for different crown-rump lengths (CRL) in the above weeks and create percentile tables. METHODS: A prospective study was conducted in the Obstetrics and Gynecology Department of the University Hospital of Ioannina, including data from women with singleton pregnancies, examined in the early pregnancy unit between November 2010 and May 2015 at a CRL of 10-27 mm. The early pregnancy scan was performed vaginally, and the NT7-9w, CRL, fetal heart rate, and mean yolk sac diameter were measured. Demographic data, including body mass index and smoking, were recorded. RESULTS: NT7-9w was measured successfully in 192 fetuses out of 210 (91.4 %), with a CRL ranging from 10-27 mm. The median maternal age was 31 (range 18-43) years, and the median CRL was 19.9 (range 10.0-27.0) mm. Considering the above measurements, we created normal values and percentiles tables of NT at 7+0 to 9+0 weeks in relation to the corresponding CRL measurement. CONCLUSION: According to the literature, this is the first attempt to measure NT in such weeks of pregnancy. NT measurement as early as 7+0 to 9+0 is feasible and normal values can be created and correlated with CRL measurements. HIPPOKRATIA 2021, 25 (4):151-155.

Lowe syndrome identified in the offspring of an oocyte donor who was an unknown carrier of a de novo mutation: a case report and review of the literature.

BACKGROUND: Oculocerebrorenal syndrome of Lowe is an X-linked disorder with very low prevalence in the general population. The OCRL gene encodes the protein phosphatidylinositol 4,5-bisphosphate-5-phosphatase, a lipid phosphatase, located in the trans-Golgi network. Point mutations in the OCRL gene cause Lowe syndrome and Dent disease, which are characterized as a multisystemic disorder. The symptoms of Lowe syndrome are expressed primarily as dysfunction of the eyes, kidneys, and the central nervous system. CASE PRESENTATION: This report describes a case of a 31-year-old Georgian woman with a de novo pathogenic mutation causing oculocerebrorenal syndrome of Lowe, who was a volunteer in an oocyte donation program for in vitro fertilization purposes, and the outcome of the treatments of this particular donor's oocyte receivers, describing the implications of the mutation for the children born as a result of the treatments. It raises important medical and ethical issues about the necessity of genetic testing of oocyte donors and the possibility of rare genetic disorders being inherited by the offspring of donors. CONCLUSION: This particular case indicates the legal, medical, and emotional risks of utilizing donor oocytes from phenotypically healthy women, whose genetic constitution is unknown in terms of being silent carriers of rare diseases. In addition, all the necessary actions were followed; the further examinations that are required are mentioned. The donor and the offspring should be further tested. The remaining cryopreserved embryos should be destroyed or preimplantation genetic testing should be performed before they are utilized. Finally, all the people involved, the treated couples and the donor, alongside her family, should follow genetic and psychological counselling.

Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project.

BACKGROUND: The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). METHODS: Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. RESULTS: In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3-126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61-1.55); P = 0.647]. Eighty DFS events (3M N = 41; 6M N = 39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68-1.63, P = 0.829). For stage III patients, 314 DFS events (3M N = 161 and 6M N = 153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81-1.42, P = 0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54-2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59-1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74-1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70-1.44). CONCLUSIONS: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01308086.

Changes in levator hiatus dimensions during pregnancy and after delivery in nulliparas: a prospective cohort study using 3D transperineal ultrasound.

PURPOSE: The purpose of this study was to investigate the changes that occur in the levator ani muscle (1) during pregnancy and (2) after labor depending on the mode of delivery in a cohort of nulliparas. MATERIALS AND METHODS: A prospective cohort longitudinal study, consisting of 84 primiparas who were examined and recruited in an antenatal clinic was conducted. All participants were submitted to a real-time three-dimensional (3D) ultrasonographic evaluation of the levator ani at (1) 12, (2) 22, and (3) 32 weeks of pregnancy (4) and 4-6 months postdelivery. The 3D volumes were acquired and stored for an offline analysis. RESULTS: Data from 59 women with at least two measurements were available for analysis. 35 women were delivered vaginally and 24 via cesarean section. There was a statistical increase in the dimensions of the levator hiatus at each pregnancy trimester when compared to the measurements of the previous trimesters. After vaginal delivery, hiatal dimensions increased compared to the third-trimester measurements; after cesarean section, hiatal dimensions decreased. CONCLUSIONS: This study supports that in primiparas, the dimensions of the levator hiatus increase significantly during pregnancy and subsequently either increase further after vaginal delivery or decrease to the first-trimester levels after cesarean section.

Does first-trimester nuchal cord affect the blood flow in the ductus venosus? A prospective observational study.

INTRODUCTION: Main objective of the present study was to investigate the association between the presence of nuchal cord (NC) and the measurement of the ductus venosus pulsatility index for veins (ductus venosus (DV) PIV). METHODS: This was a prospective study of 1974 singleton pregnancies that underwent first-trimester screening at 11-13+6 gestational weeks. Color Doppler was used to demonstrate the presence of a NC in all cases and the DV PIV was calculated routinely, as part of the standard scan. The association between the presence of a NC and the DV PIV was then examined overall and at each gestational week. RESULTS: A NC was demonstrated in 17.1% of cases. The incidence of nuchal cord was significantly higher at 13-13+6 weeks (24.7%, n = 119) compared to the one at 12-12+6 (16.5%, n = 192) and 11-11+6 weeks (7.9%, n = 26) (p < .001). No significant correlation was found between NC presence and DV PIV (p = .344). The DV PIV was 0.99 (± 0.15) for patients without NC versus 0.99 (± 0.15) for patients with NC (p = .34). CONCLUSIONS: There was no association between the presence of a NC at 11-13+6 gestational weeks and the DV PIV.

Risks of miscarriage or preterm delivery in trichorionic and dichorionic triplet pregnancies with embryo reduction versus expectant management: a systematic review and meta-analysis.

STUDY QUESTION: Is pregnancy outcome in triplet pregnancies improved with embryo reduction (ER) to twins compared to expectant management? SUMMARY ANSWER: In trichorionic triplet pregnancies, ER to twins reduces the risk of preterm birth (<34 weeks) without significantly increasing the risk of miscarriage (<24 weeks), whereas in dichorionic triplet pregnancies, the results are inconclusive. WHAT IS KNOWN ALREADY: Triplet pregnancies are associated with a high risk of miscarriage and preterm birth. ER can ameliorate these conditions in higher order multiple gestations but is still controversial in triplets. STUDY DESIGN, SIZE, DURATION: This study aimed to conduct a systematic review, following the PRISMA guidelines, and critically appraise ER at 8-14 weeks of gestation in both trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) pregnancies. Selective ER to twins was compared with expectant management, focusing on the risks of miscarriage and preterm birth. The computerized database search was performed on 8 January 2017. Overall, from 25 citations of relevance, eight studies with a total of 249 DCTA and 1167 TCTA pregnancies fulfilled the inclusion criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive computerized systematic literature search of all English language studies between 2000 and 2016 was performed in PubMed, EMBASE, Scopus, Evidence Based Medicine Reviews (Cochrane Database and Cochrane Central Register of Controlled Trials) and Google Scholar. Relevant article reference lists were hand searched. The management options were compared for rates of miscarriage <24 weeks and preterm birth <34 weeks. Only studies with both expectant management and ER to twins were included in the analysis. The quality of each individual article was critically appraised and appropriate statistical methods were used to extract results. MAIN RESULTS AND THE ROLE OF CHANCE: In TCTA pregnancies managed expectantly (n = 501), the rates of miscarriage and preterm birth were 7.4 and 50.2%, respectively. Meta-analysis demonstrated that ER to twins in TCTA pregnancies (n = 666) was associated with a lower risk (17.3 versus 50.2%) of preterm birth (RR = 0.36, 95% CI: 0.28-0.48), whereas the risk of miscarriage (8.1% versus 7.4%) did not significantly increase (RR = 1.08, 95% CI: 0.58-1.98). In DCTA triplets managed expectantly (n = 200), the rates of miscarriage and preterm birth were 8.5 and 51.9%, respectively. Although the meta-analysis was inconclusive, it suggested that ER to twins in DCTA triplets, either of the foetus with a separate placenta (n = 15) or one of the monochorionic pair (n = 34), was neither significantly associated with an increased risk of miscarriage (8.5 versus 13.3%, P = 0.628 and RR = 1.22, 95% CI: 0.38-3.95, respectively) nor with a lower risk of preterm birth (51.9 versus 46.2%, P = 0.778 and RR = 0.5, 95% CI: 0.04-5.7, respectively). LIMITATIONS, REASONS FOR CAUTION: No randomized controlled trials of ER versus expectant management in TCTA or DCTA pregnancies were identified from our literature search. We were able to include only a handful of papers with small sample sizes and suffering from bias, and non-English publications were missed. Irrespective of the strict inclusion and exclusion criteria, publication bias was evident. WIDER IMPLICATIONS OF THE FINDINGS: The greatest strength of our systematic review is that, contrary to the existing literature, it only included studies with both the intervention and expectant arm. Our results are in agreement with current literature. In TCTA pregnancies, ER to twins is associated with a lower risk of preterm birth but is not associated with a higher risk of miscarriage. In the absence of a randomized trial, the data from systematic reviews appear to be the best existing evidence for counselling in the first trimester on the different options available. Finally, in DCTA pregnancies, indications exist that ER (of one of the MC pair) to twins could possibly reduce the risk of preterm birth without increasing the risk of miscarriage. STUDY FUNDING/COMPETING INTEREST(S): None to declare. REGISTRATION NUMBER: N/A.

RAG Recombinase as a Selective Pressure for Genome Evolution.

The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an ongoing discussion, in particular regarding the counter-selection of sequences resembling the RSS and the modifications of epigenetic regulation at these potential cryptic sites. Here, we describe a new bioinformatics tool to map potential RAG targets in all jawed vertebrates. We show that our REcombination Classifier (REC) outperforms the currently available tool and is suitable for full genomes scans from species other than human and mouse. Using the REC, we document a reduction in density of potential RAG targets at the transcription start sites of genes co-expressed with the rag genes and marked with high levels of the trimethylation of the lysine 4 of the histone 3 (H3K4me3), which correlates with the retention of functional RAG activity after the horizontal transfer.

Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

BACKGROUND: Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide. PATIENTS AND METHODS: In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic G-CSF support (FEC → D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate. RESULTS: Six hundred and fifty women were randomized to either FEC → D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC → D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC → D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths. CONCLUSIONS: This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC → D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer. CLINICALTRIALSGOV: NCT01985724.

Fluorescence lifetime imaging of optically levitated aerosol: a technique to quantitatively map the viscosity of suspended aerosol particles.

We describe a technique to measure the viscosity of stably levitated single micron-sized aerosol particles. Particle levitation allows the aerosol phase to be probed in the absence of potentially artefact-causing surfaces. To achieve this feat, we combined two laser based techniques: optical trapping for aerosol particle levitation, using a counter-propagating laser beam configuration, and fluorescent lifetime imaging microscopy (FLIM) of molecular rotors for the measurement of viscosity within the particle. Unlike other techniques used to measure aerosol particle viscosity, this allows for the non-destructive probing of viscosity of aerosol particles without interference from surfaces. The well-described viscosity of sucrose aerosol, under a range of relative humidity conditions, is used to validate the technique. Furthermore we investigate a pharmaceutically-relevant mixture of sodium chloride and salbutamol sulphate under humidities representative of in vivo drug inhalation. Finally, we provide a methodology for incorporating molecular rotors into already levitated particles, thereby making the FLIM/optical trapping technique applicable to real world aerosol systems, such as atmospheric aerosols and those generated by pharmaceutical inhalers.

Direct imaging of changes in aerosol particle viscosity upon hydration and chemical aging.

Organic aerosol particles (OA) play major roles in atmospheric chemistry, climate, and public health. Aerosol particle viscosity is highly important since it can determine the ability of chemical species such as oxidants, organics or water to diffuse into the particle bulk. Recent measurements indicate that OA may be present in highly viscous states, however, diffusion rates of small molecules such as water are not limited by these high viscosities. Direct observational evidence of kinetic barriers caused by high viscosity and low diffusivity in aerosol particles were not available until recently; and techniques that are able to dynamically quantify and track viscosity changes during atmospherically relevant processes are still unavailable for atmospheric aerosols. Here we report quantitative, real-time, online observations of microscopic viscosity changes in aerosol particles of atmospherically relevant composition, using fluorescence lifetime imaging (FLIM) of viscosity. We show that microviscosity in ozonated oleic acid droplets and secondary organic aerosol (SOA) particles formed by ozonolysis of myrcene increases substantially with decreasing humidity and atmospheric oxidative aging processes. Furthermore, we found unexpected heterogeneities of microviscosity inside individual aerosol particles. The results of this study enhance our understanding of organic aerosol processes on microscopic scales and may have important implications for the modeling of atmospheric aerosol growth, composition and interactions with trace gases and clouds.

Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria.

KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors.

Three-dimensional versus two-dimensional ultrasound for fetal nasal bone evaluation in the second trimester.

OBJECTIVES: To compare two-dimensional with three-dimensional ultrasound evaluation of the fetal nasal bone in the second trimester. METHODS: A prospective, non-interventional study was conducted, in 55 singleton fetuses, between 18 and 24 weeks' gestation. Fetal nasal bone length was measured in the midsagittal plane by two-dimensional imaging and in the midsagittal and coronal plane with three-dimensional ultrasound. All three measurements were compared with one another using one-way repeated samples-measures ANOVA and paired samples t-test. RESULTS: The average fetal nasal bone length (mean ± SD) as determined by the three methods was 7.01 ± 0.94 mm for the two-dimensional midsagittal, 6.96 ± 1.34 mm for the three-dimensional midsagittal, and 6.98 ± 1.32 mm for the three-dimensional coronal plane; comparisons between one another were not statistically significant. Unilateral hypoplasia and bifid shape of the fetal nasal bone were detected in 8.2% and 20.4% of cases, respectively, by three-dimensional ultrasound, whereas all cases evaded detection with two-dimensional ultrasound (p < 0.001 and p = 0.001, respectively). CONCLUSIONS: Fetal nasal bone length measured with two-dimensional ultrasound does not differ significantly from three-dimensional measurements. However, three-dimensional ultrasound is superior in detecting unilateral nasal bone hypoplasia or absence and in assessing fetal nasal bone shape. Hence, fetal nasal bone examination in the second trimester should include three-dimensional ultrasound evaluation.

[Diagnostics and therapy of chronic stable coronary artery disease : new guidelines of the European Society of Cardiology]. / Diagnostik und Therapie der chronisch stabilen koronaren Herzkrankheit : Neue Empfehlungen der Europäischen Gesellschaft für Kardiologie.

The European Society of Cardiology (ESC) guidelines on the management of stable coronary artery disease published in 2013 give practical recommendations for diagnostics and therapy. The approach depends on the clinical picture and symptoms of the patient, the severity and extent of ischemia, the degree and location of coronary stenoses, additional cardiac findings and finally on non-cardiac comorbidities. The selection of suitable diagnostic tools is based on the tabulated pretest probability for the presence of coronary artery disease which plays an important and central role in the diagnostic algorithm. An invasive approach is recommended only in patients with severe angina, i.e. a Canadian Cardiovascular Society (CCS) angina grading scale of ≥ CCS3 or in patients who are at high risk for death or myocardial infarction based on the results of the test used for detection of ischemia. Detailed therapeutic recommendations are given for medicinal and interventional or surgical therapy. Medicinal therapy includes drugs both for relief of symptoms and prevention of cardiovascular events. Recommendations are also given for the use of new antianginal drugs. A PCI is only indicated in vessels causing ischemia which can be verified by using fractional flow reserve measurements. The indications for PCI now also include patients with a low SYNTAX score and multivessel disease or left main stenosis; however, the optimal strategy should be individually determined in heart team discussions.

[Dizziness and syncope : clinical case examples]. / Schwindel und Synkope : Klinische Fallbeispiele.

Syncope is defined as a transient, self-limiting loss of consciousness and postural tone due to transient global cerebral hypoperfusion. After syncope the following questions have to be answered: was it a syncopal episode, has the etiological diagnosis been determined, are there data suggestive of a high risk of cardiovascular events or death and what are the therapeutic options? Therefore, a standardized diagnostic work-up is necessary. This diagnostic work-up with differential diagnostic considerations is given for three clinical cases: a 52-year-old man experienced syncope while driving a car and on the morning of the same day syncope had previously occurred while in a standing position. The initial cardiological and neurological evaluation revealed no pathological findings but after implantation of a loop recorder a further syncope with a sinus arrest of 17 s occurred 1 year later. The patient received a single chamber pacemaker. The second case is a 79-year-old female with Parkinson's disease for many years and a primary autonomic dysfunction leading to dizziness and syncope due to pronounced blood pressure fluctuations with hypertensive and hypotensive phases. The last patient is a 22-year-old female with postural orthostatic tachycardia syndrome and recurrent syncope. The diagnostic evaluation and treatment proved to be difficult.

Conjugatable water-soluble Pt(II) and Pd(II) porphyrin complexes: novel nano- and molecular probes for optical oxygen tension measurement in tissue engineering.

Measurement of oxygen tension in compressed collagen sheets was performed using matrix-embedded optical oxygen sensors based on platinum(II) and palladium(II) porphyrins supported on polyacrylamide nanoparticles. Bespoke, fully water-soluble, mono-functionalised Pt(II) and Pd(II) porphyrin complexes designed for conjugation under mild conditions were obtained using microwave-assisted metallation. The new sensors display a linear response (1/τ vs. O2) to varying oxygen tension over a biologically relevant range (7.0 × 10(-4) to 2.7 × 10(-1) mM) in aqueous solutions; a behaviour that is maintained following conjugation to polyacrylamide nanoparticles, and following embedding of the nanosensors in compressed collagen sheets, paving the way to innovative approaches for real-time resolution of oxygen gradients throughout 3D matrices useful for tissue regeneration.

Cense: a tool to assess combined exposure to environmental health stressors in urban areas.

This paper describes the structure of the Combined Environmental Stressors' Exposure (CENSE) tool. Individuals are exposed to several environmental stressors simultaneously. Combined exposure represents a more serious hazard to public health. Consequently, there is a need to address co-exposure in a holistic way. Rather than viewing chemical and physical health stressors separately for decision making and environmental sustainability considerations, the possibility of an easy-to-comprehend co-exposure assessment is herein considered. Towards this aim, the CENSE tool is developed in the programming environment of Delphi. The graphical user's interface facilitates its tractable application. Studying different scenarios is easy since the execution time required is negligible. The tool incorporates co-exposure indicators and takes into account the potential dose of each chemical stressor by considering the physical activities of each citizen in an urban (micro)environment. The capabilities of the CENSE tool are demonstrated through its application for the case of Thessaloniki, Greece. The test case highlights usability and validation insights and incorporates health stressors and local characteristics of the area considered into a well identified user/decision maker interface. The main conclusion of the work reported is that a decision maker can trust CENSE for urban planning and environmental sustainability considerations, since it supports a holistic assessment of the combined potential damage attributed to multiple health stressors. CENSE abandons the traditional approach of viewing chemical and physical stressors separately, which represents the most commonly adopted strategy in real life decision support cases.