Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

Accuracy of ultrasound for predicting pathologic response during neoadjuvant therapy for breast cancer

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no‐pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO‐2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/?) and 2.65 (ypT0/is/1a,ypN+/?). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO‐2D and RECIST; WHO‐1D was highly specific with low sensitivity. Sensitivity was highest for WHO‐2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO‐1D). Adding US to models including patient variables (age, T‐stage, histology and subtype) improved AUCs for predicting pCR by 2–3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long‐term survival. WHO‐2D and RECIST maximise sensitivity; WHO‐1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.     

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.     

Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin and quercetin

Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with antiinflammatory, antiischemic, vasodilating and chemoprotective properties. In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubicin-induced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes. After preincubation of cardiomyocytes with the test compounds for 1 h the cardiomyocytes were treated with the toxic agent, doxorubicin (100 micro M for 8 h). Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production. Cytoprotection was concentration dependent for baicalein > luteolin congruent with apigenin > quercetin > kaempferol. All test compounds had signi fi cantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy. In microsomes/mitochondria the IC(50) values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/73.1 +/- 6.4 mM, respectively. The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E(p/2)). Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds.     

The presence of monoiodinated derivates of daidzein and genistein in human urine and its effect on thyroid gland function

Dietary supplements used by women during menopause are usually based on plant extracts containing isoflavonoids, daidzein and genistein. Genistein is a known inhibitor of many enzymes, including thyroid peroxidase (TPO). In the thyroid follicle, genistein acts as its alternate substrate for the formation of genistein iodinated derivatives. The aim of this study was to search for daidzein- and genistein-iodinated derivatives in urine of isoflavonoid-supplemented women. Additionally, selected phytoestrogens, steroid and thyroid hormones before and after three months of phytoestrogen supplementation were estimated. Urinary levels of free phytoestrogen increased significantly after therapy. They ranged between 0.3–1600, 0.6–670 and 0–206 nmol/L for daidzein, genistein and S-equol, respectively. Monoiodinated derivatives of genistein were observed (0–504 pmol/L) in 60% of the investigated samples. Steroid and thyroid hormone levels were within the normal range and were not significantly altered. The presence of monoiodinated derivates in human urine confirmed that genistein and daidzein may enter human thyroid follicles and influence TPO. Since the levels of the free thyroid hormones were not affected, we propose that the use of phytoestrogen dietary supplements is not associated with the development of thyroid-gland disorders in subjects with adequate iodine intake.     

捷克中医药发展现状与分析

捷克作为欧洲内陆的议会共和制国家,实施强制保险模式以保障民众健康。导致人口死亡的主要疾病为缺血性心脏病、脑卒中和肺癌,而糖尿病、AD及COPD近年来发病率显著增加。捷克的传统医学包括巴赫花疗法、特异性免疫调节自我疗法、法国耳针治疗等。中医药在捷克具有一定的接受度,尤其是针灸已在神经性疾病中得到广泛应用。但中草药在捷克的使用受到限制,且中医药执业尚未合法化。建议深化多层次、多领域交流合作,并通过加强高水平中医药学位教育,加大中药与非药物疗法宣传和普及力度,推动中医药在捷克的发展。     

Sister-to-sister oocyte donation: couples’ experiences with regard to genetic ties

Objective: This study aimed to gain an in-depth understanding of the experiences of genetic ties in intrafamily oocyte donation families. Background: Previous research has shown that most mothers have a good and stable relationship with their donor. Little is known about the meaning of the difference in genetic ties for parents who conceived through sister-to-sister oocyte donation. Methods: An Interpretative Phenomenological Analysis was performed and focused on both individual experiences and couple experiences with regard to genetic ties. Ten participants were recruited via an infertility clinic and took part in semistructured couple interviews. Results: Our analysis revealed that the donation was seen as a way to equal genetic parenthood. Participants struggled with this prevailing ideal of genetic parenthood and questioned the legitimacy of their motherhood. Several dynamics were identified when couples tried to deal with the imbalance in genetic ties: they acknowledged each other, convinced one another, or pushed away the difference in genetic ties. Couples also managed the presence of a genetic tie with the donor by negotiating the closeness in their family relationships. Conclusion: The lack of a full genetic tie remained a meaningful absence for some mothers and the way couples dealt with this varied. We plead that the option of post-donation care should be offered to support couples with the complexities they try to deal with.     

Can MRI Be Used as a Sole Diagnostic Modality in Determining Clinical Stage in Cervical Cancer?

ObjectiveThe objective of this study was to compare staging by MRI to clinical staging in patients with cervical cancer and to determine the histological accuracy of staging by MRI and examination under anesthesia (EUA) in early stage disease.MethodsThis was a retrospective cohort study of patients diagnosed with cervical cancer between 2010 and 2020 at the Radboud University Medical Centre, the Netherlands. Pretreatment stage (FIGO 2009) by MRI was compared with staging by EUA. Diagnostic accuracy in terms of sensitivity, specificity, positive, and negative predictive value was calculated for MRI and EUA in patients undergoing surgery (early stage disease) with histological results as a reference standard.ResultsA total of 358 patients were included in the study and MRI-based stage differed from EUA stage in 30.7%. In 12.3% this meant a discrepancy in treatment assignment between MRI and EUA. Diagnostic accuracy of MRI in terms of sensitivity and specificity for detecting early stage disease was comparable to EUA in surgical patients. Further analyses showed that premenopausal status, early stage disease and a tumor diameter of <2 cm were associated with improved comparability of MRI and EUA (98%).ConclusionThere is still a large discrepancy between MRI and EUA. In patients with suspected early stage disease, diagnostic accuracy of MRI is similar to EUA, especially for premenopausal women with early stage disease and a tumor diameter of <2 cm.     

Accuracy of palatal orthodontic mini-implants placed by conventionally or CAD/CAM-based surgical guides: a comparative in vitro study

ObjectivesTo investigate and compare the transfer accuracy of five different surgical guides (SGs) for the insertion of orthodontic mini-implants (OMIs) in the anterior palate.Materials and MethodsStereolithographic files of 10 maxillary patient models and their corresponding lateral cephalograms were virtually matched and used for planning the position of two parallel OMIs in the paramedian region of the anterior palate. For each patient model, three 3-dimensional (3D)–printed and two conventional SGs were manufactured from different materials, and a total of 96 OMIs were transferred to the anterior palates of the respective 50 molded resin models. The planned (T0) and the actual (T1) OMI positions were analyzed and compared after superimposition of the digitized models. The deviations between the OMI positions in T0 and T1 were described as the distance between the head and the tip, respectively, of each OMI in millimeters and the deviating angle between the OMI axes for each patient and SG.ResultsThe conventionally manufactured SGs of Pattern Resin LS (GC Europe N.V., Leuven, Belgium) showed the highest linear and angular transfer accuracy for the insertion of OMIs. The highest deviations were found with the SGs made of IMPRIMO LC Splint (3D-printed; Scheu-Dental, Iserlohn, Germany) and Memosil 2 (conventional SG; Kulzer, Hanau, Germany).ConclusionsThe 3D-printed SGs did not reach the accuracy of the conventional SGs made of Pattern Resin but may provide sufficient accuracy for palatal OMI placement.