Revisiting the evolution of the Hippocratic Oath in obstetrics and gynecology.

Hippocrates, an influential figure in ancient Greek medicine, is best known for his lasting contribution, the Hippocratic Oath, which includes a significant message about obstetrics and gynecology. Given the Oath's status as a widely regarded ethical code for medical practice, it requires critical evaluation. The message of the Oath, as it related to obstetrics and gynecology, is expressed in ancient Greek by the phrase "οὐδὲ γυναικὶ πεσσὸν φθόριον δώσω" which translates directly to "I will not give to any woman a harming pessary." The words fetus and abortion were not present in the original Greek text of the Oath. Yet, this message of the Hippocratic Oath has been interpreted often as a prohibition against abortion. In this article, we present a critical linguistic and historical analysis and argue against the notion that the Hippocratic Oath was prohibiting abortion. We provide evidence that the words "foetum" (fetus) and "abortu" (abortion) were inserted in the Latin translations of the Oath, which then carried on in subsequent English versions. The addition of the words "fetus" and "abortion" in the Latin translations significantly altered the Oath's original meaning. Unfortunately, these alterations in the translation of the Hippocratic Oath have been accepted over the years because of cultural, religious, and social reasons. We assert that because the original Hippocratic Oath did not contain language related to abortion, it should not be construed as prohibiting it. The interpretation of the Oath should be based on precise and rigorous translation and speculative interpretations should be avoided.

Bread Wheat Landraces Adaptability to Low-Input Agriculture.

Bread wheat landraces were an important source of biodiversity used in agriculture before the widespread adoption of high-yielding commercial cultivars adapted to high inputs. Could future agriculture exploit these landraces in different cropping systems in organic or lower-input environments? A two-year field trial was conducted to evaluate grain yield, agronomic performance, and grain quality of bread wheat landraces under different cropping systems, including low-input/organic/conventional environments. Significant variability was found for almost all characteristics among landraces, which makes landraces valuable sources of genetic variation for breeding programs aimed at achieving high and consistent production as well as high-quality products in low-input/organic environments. Additionally, landraces play a crucial role in expanding the genetic diversity of cultivated bread wheat and mitigating biodiversity erosion, thereby enabling crops to better withstand the challenges of low-input/organic agriculture. The landrace "Xilokastro Lamias" had the highest yield among the landraces evaluated in the first growing season (2.65 t·ha-1) and one of the highest yields (2.52 t·ha-1) of all genotypes in the second growing season, which shows promising potential as a starting material in breeding programs targeting high and stable yields. GGE biplot analysis identified the landrace "Xilokastro Lamias", along with commercial cultivars "Yecora E" and "Panifor", as suitable candidates for direct use in low-input/organic wheat farming systems to achieve enhanced productivity. In the conventional environment (C2-IPGRB), commercial cultivars showed the highest values (3.09 to 3.41 ton·ha-1). Of the landraces, only the X4 showed a high GY (3.10 ton·ha-1) while the other landraces had ~33-85% lower yield. In the organic environment (O2-IPGRB), the highest productivity was found in the commercial cultivar X5 and the landrace X4. Commercial cultivars X8 and X7 showed ~68% reduction in GY in the organic environment compared to the conventional, while this reduction was half for the landraces. Finally, the reduction in grain yield between conventional and organic environments was observed to be 45% for commercial cultivars, while it was only half for landraces. This finding confirms the adaptability of landraces to organic agriculture.

Evaluation of a dill (Anethum graveolens L.) gene bank germplasm collection using multivariate analysis of morphological traits, molecular genotyping and chemical composition to identify novel genotypes for plant breeding.

Dill (Anethum graveolens L.) is an aromatic herb widely used in the food industry, with several commercial cultivars available with different qualitative characteristics. Commercial cultivars are usually preferred over landraces due to their higher yield and also the lack of improved landraces than can be commercialized. In Greece, however, traditional dill landraces are cultivated by local communities. Many are conserved in the Greek Gene Bank and the aim here was to investigate and compare the morphological, genetic, and chemical biodiversity of twenty-two Greek landraces and nine modern/commercial cultivars. Multivariate analysis of the morphological descriptors, molecular markers, and essential oil and polyphenol composition revealed that the Greek landraces were clearly distinguished compared with modern cultivars at the level of phenological, molecular and chemical traits. Landraces were typically taller, with larger umbels, denser foliage, and larger leaves. Plant height, density of foliage, density of feathering as well as aroma characteristics were desirable traits observed for some landraces, such as T538/06 and GRC-1348/04, which were similar or superior to those of some commercial cultivars. Polymorphic loci for inter-simple sequence repeat (ISSR) and start codon targeted (SCoT) molecular markers were 76.47% and 72.41% for landraces, and 68.24% and 43.10% for the modern cultivars, respectively. Genetic divergence was shown, but not complete isolation, indicating that some gene flow may have occurred between landraces and cultivars. The major constituent in all dill leaf essential oils was α-phellandrene (54.42-70.25%). Landraces had a higher α-phellandrene and dill ether content than cultivars. Two dill landraces were rich in chlorogenic acid, the main polyphenolic compound determined. The study highlighted for the first-time Greek landraces with desirable characteristics regarding quality, yield, and harvest time suitable for breeding programs to develop new dill cultivars with superior features.

The Evaluation of Common Bean (Phaseolus vulgaris L.) Genotypes under Water Stress Based on Physiological and Agronomic Parameters.

Drought affects common bean productivity, and the severity of its impact is expected to increase due to climate change. The use of versatile genotypes could contribute to securing future bean production. This study investigates the adaptability of 10 common bean genotypes of indeterminate growth type under water scarcity conditions by measuring agronomic and physiological parameters. The evaluation occurs under irrigation treatments applied at two different phenological stages (anthesis (WDA) and seed filling initiation (WDSF)). The recorded adaptabilities of the genotypes (G) showed that G10 produced the highest overall seed yield in the normal irrigation (NI) (197.22 g plant-1) and WDA (192.78 g plant-1), while the G6 had the highest yield at WDSF (196.71 g plant-1). For the genotype's average mean, chlorophyll content decreased by 10.5% under drought at WDSF. Net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (E) were reduced at WDA by 53%, 80.8%, and 61.4% and at WDSF by 43.75%, 57.7%, and 36%, respectively, while relative water content (RWC) reduced by 16.48%, on average, for both stages. G10 and G6 showed adaptability when water scarcity occurred at an early (WDA) or later stage (WDSF), respectively, providing insights into using germplasm resources to cope with the drought effect.

A Four-Probiotics Regimen Combined with A Standard Helicobacter pylori-Eradication Treatment Reduces Side Effects and Increases Eradication Rates.

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.

Bioactive Components and Antioxidant Activity Distribution in Pearling Fractions of Different Greek Barley Cultivars.

In this study, three pearling fractions, namely bran, dehulled grains and pearled grains, derived from fourteen hulled and one hull-less Greek barley cultivars (Hordeum vulgare L.), were analyzed for the protein, ash, ß-glucan, phenolic compounds and tocols contents. High variations appeared in the bioactive contents across the barley cultivars and fractions as well. The protein and ash contents decreased from the outer to the inner layers, whereas ß-glucans presented an inverse trend. The highest protein and ß-glucan contents were in the hull-less cultivar; however, one hulled cultivar (Sirios) exhibited similar ß-glucan content, while another (Constantinos) had even higher protein content. The results also revealed that functional compounds were mainly located in bran fraction. Similar trends were also noted for the antioxidant activity. Ferulic acid was the primary phenolic acid in all fractions, followed by sinapic and p-coumaric acids that were dominant in bound form. However, oligomeric flavonoids, such as prodelphinidin B3, catechin, and procyanidin B2, were more abundant in free form. Overall, this study highlights that different barley cultivars can provide pearling flour fractions of varying composition (nutrients and bioactives), which have the potential to serve as nutritionally valuable ingredients in formulations of cereal-based functional food products.

Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations.

Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages.

Induction of DNA damage and apoptosis in human leukemia cells by efavirenz.

As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml. Cell death induced by efavirenz was caused by apoptosis, as shown by FACScan analysis (Annexin binding) and western blot analysis (cleavage of caspases and PARP). Western blot analyses also revealed a pronounced activation and phosphorylation of the DNA damage marker proteins p53, chk2 and H2AX, indicating DNA replication and genomic integrity as primary targets of efavirenz in leukemia cells.

Effect of probiotics on vaginal health in pregnancy. EFFPRO, a randomized controlled trial.

BACKGROUND: Preterm delivery is a leading cause of neonatal morbidity and death. It often results from chorioamnionitis, which is a complication of bacterial vaginosis. Probiotics are effective in the treatment of bacterial vaginosis in women who were not pregnant; studies in pregnant woman are missing. OBJECTIVE: The purpose of this study was to evaluate whether an oral probiotic food supplement supports the maintenance or restoration of a normal vaginal microbiota during pregnancy. STUDY DESIGN: We conducted a randomized, placebo-controlled, triple-blind, parallel group trial. Oral Lactobacillus rhamnosus GR-1and L reuteri RC-14 (109 colony-forming units) or placebo were administered for 8 weeks to women with <12 completed weeks of pregnancy. Participants were enrolled at Tuebingen University Hospital and 10 recruiting gynecologic practices. Vaginal swabs were taken before and after intervention and analyzed according to the Nugent scoring system. Telephone interviews were performed before and after intervention and after delivery. Primary outcome was the proportion of swabs with normal Nugent score (<4) after intervention, compared by Fisher's exact test in an intention-to-treat analysis. RESULTS: Three hundred twenty pregnant women were enrolled. Vaginal swabs were analyzed from 290 women before and 271 women after intervention. The proportion of normal vaginal microbiota decreased from 82.6 to 77.8% in the treatment group and from 79.1 to 74.3% in the placebo group, with no significant difference across groups after intervention (P=.297). CONCLUSION: Oral probiotics may be suitable for implementation in antenatal care but, as administered here, had no effect on vaginal health during mid gestation. Other application routes or probiotic preparations may be more effective in supporting vaginal microbiota during pregnancy.

Expression of Activin During and After Chemotherapy in Peripheral Blood of Patients with Primary Breast Cancer.

BACKGROUND/AIM: Activins are dimeric glycoproteins that play a significant role in reproduction and in endocrine-active tumors. The aim of this study was to evaluate the potential correlation between the concentration of activins (activin A, activin B, and activin AB) in patients receiving adjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: The serum concentration of activins in 30 patients receiving chemotherapy within the German SUCCESS A study was analyzed using different enzyme-linked immunosorbent assays at three time points: After primary surgery, but before chemotherapy; 4 weeks after the end of chemotherapy; and 2 years after chemotherapy during recurrence-free follow-up. RESULTS: The activin concentration decreased in all patients after chemotherapy. Premenopausal patients had significantly lower concentrations of activin AB during follow-up than postmenopausal women (p=0.037). Thirteen out of 16 premenopausal patients developed chemotherapy-related amenorrhea (CRA) but did not significantly differ in their activin concentrations compared to the other premenopausal women. A positive human epidermal growth factor receptor 2/neu status was associated with a significant reduction of activin AB concentration (p=0.02), and trastuzumab treatment correlated with significantly decreased activin A concentration (p=0.012). CONCLUSION: Serial measurements of activin A concentration might be used for monitoring trastuzumab treatment. A sudden increase of activin concentration could be an early indicator of disease recurrence.

Addressing huge spatial heterogeneity induced by virus infections in lentil breeding trials.

BACKGROUND: Spatial heterogeneity can have serious effects on the precision of field experimentation in plant breeding. In the present study the capacity of the honeycomb design (HD) to sample huge spatial heterogeneity was appraised. For this purpose, four trials were conducted each comprising a lentil landrace being screened for response to viruses. RESULTS: Huge spatial heterogeneity was reflected by the abnormally high values for coefficient of variation (CV) of single-plant yields, ranging 123-162 %. At a given field area, increasing the number of simulated entries was followed by declined effectiveness of the method, on account of the larger circular block implying greater intra-block heterogeneity; a hyperbolic increasing pattern of the top to bottom entry mean gap (TBG) indicated that a number of more than 100 replicates (number of plants per entry) is the crucial threshold to avoid significant deterioration of the sampling degree. Nevertheless, the honeycomb model kept dealing with variation better than the randomized complete block (RCB) pattern, thanks to the circular shape and standardized type of block that ensure the less possible extra heterogeneity with expanding the area of the block. CONCLUSIONS: Owing to the even and systematic entry allocation, breeders do not need to be concerned with the extra spatial heterogeneity that might induce the extra surface needed to expand the size of the block when many entries are considered. Instead, they could improve accuracy of comparisons with increasing the number of replicates (circular blocks) despite the concomitant greater overall spatial heterogeneity.

Efavirenz Causes Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Endothelial Cells.

The non-nucleoside reverse transcriptase inhibitor efavirenz is a widely prescribed antiretroviral drug used in combined antiretroviral therapy. Despite being an essential and life-saving medication, the required lifelong use of HIV drugs has been associated with a variety of adverse effects, including disturbances in lipid metabolism and increased cardiovascular risk. Efavirenz belongs to those HIV drugs for which cardiovascular and endothelial dysfunctions have been reported. It is here shown that elevated concentrations of efavirenz can inhibit endothelial meshwork formation on extracellular matrix gels by normal and immortalized human umbilical vein cells. This inhibition was associated with an increase in oxidative stress markers, endoplasmic reticulum (ER) stress markers, and autophagy. Induction of ER stress occurred at pharmacologically relevant concentrations of efavirenz and resulted in reduced proliferation and cell viability of endothelial cells, which worsened in the presence of elevated efavirenz concentrations. In combination with the HIV protease inhibitor nelfinavir, both oxidative stress and ER stress became elevated in endothelial cells. These data indicate that pharmacologically relevant concentrations of efavirenz can impair cell viability of endothelial cells and that these effects may be aggravated by either elevated concentrations of efavirenz or by a combined use of efavirenz with other oxidative stress-inducing medications.

Indications for and Risks of Elective Cesarean Section.

BACKGROUND: Rates of cesarean section have risen around the world in recent years. Accordingly, much effort is being made worldwide to understand this trend and to counteract it effectively. A number of factors have been found to make it more likely that a cesarean section will be chosen, but the risks cannot yet be clearly defined. METHODS: This review is based on pertinent publications that were retrieved by a selective search in the PubMed, Scopus, and DIMDI databases, as well as on media communications, analyses by the German Federal Statistical Office, and guidelines of the Association of Scientific Medical Societies in Germany (AWMF). RESULTS: The increased rates of cesarean section are thought to be due mainly to changed risk profiles both for expectant mothers and for their yet unborn children, as well as an increase in cesarean section by maternal request. In 1991, 15.3% of all newborn babies in Germany were delivered by cesarean section; by 2012, the corresponding figure was 31.7%, despite the fact that a medical indication was present in less than 10% of all cases. This development may perhaps be explained by an increasing tendency toward risk avoidance, by risk-adapted obstetric practice, and increasing media attention. The intraoperative and postoperative risks of cesarean section must be considered, along with complications potentially affecting subsequent pregnancies. CONCLUSION: Scientific advances, social and cultural changes, and medicolegal considerations seem to be the main reasons for the increased acceptibility of cesarean sections. Cesarean section is, however, associated with increased risks to both mother and child. It should only be performed when it is clearly advantageous.

Analysis of endoplasmic reticulum stress in placentas of HIV-infected women treated with protease inhibitors.

Combined antiretroviral therapy has proven efficacy in decreasing vertical HIV transmission. However, endoplasmic reticulum stress is a known side effect of HIV protease inhibitors. We investigated endoplasmic reticulum stress in placentas of HIV-infected and uninfected mothers by PCR-based splicing analysis of the specific endoplasmic reticulum stress marker XBP1 in post-delivery placental samples of uninfected mothers and in HIV-infected mothers taking antiretroviral therapy. No elevated XBP1 splicing could be detected in placentas of uninfected mothers and most of the mothers receiving combined anti-retroviral therapy. However, markedly elevated XBP1 splicing was found in the placentas of three individuals on combined antiviral therapy, all receiving lopinavir or atazanavir. In vitro experiments confirmed induction of endoplasmic reticulum stress by lopinavir and atazanavir in trophoblast-derived cell lines. Since endoplasmic reticulum stress occurred in selective patients only, individual differences in susceptibility of HIV-infected mothers to protease inhibitor induced endoplasmic reticulum stress can be postulated.

Observational study assessing demographic, economic and clinical factors associated with access and utilization of health care services of patients with multiple sclerosis under treatment with interferon beta-1b (EXTAVIA).

Multiple sclerosis (MS) results in an extensive use of the health care system, even within the first years of diagnosis. The effectiveness and accessibility of the health care system may affect patients' quality of life. The aim of the present study was to evaluate the health care resource use of MS patients under interferon beta-1b (EXTAVIA) treatment in Greece, the demographic or clinical factors that may affect this use and also patient satisfaction with the health care system. Structured interviews were conducted for data collection. In total, 204 patients (74.02% females, mean age (SD) 43.58 (11.42) years) were enrolled in the study. Analysis of the reported data revealed that during the previous year patients made extensive use of health services in particular neurologists (71.08% visited neurologists in public hospitals, 66.67% in private offices and 48.53% in insurance institutes) and physiotherapists. However, the majority of the patients (52.45%) chose as their treating doctor private practice neurologists, which may reflect accessibility barriers or low quality health services in the public health system. Patients seemed to be generally satisfied with the received health care, support and information on MS (84.81% were satisfied from the information provided to them). Patients' health status (as denoted by disease duration, disability status and hospitalization needs) and insurance institute were found to influence their visits to neurologists. Good adherence (up to 70.1%) to the study medication was reported. Patients' feedback on currently provided health services could direct these services towards the patients' expectations.

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system.

The family of metastasis-associated (MTA) genes is a small group of transcriptional co-regulators which are involved in various physiological functions, ranging from lymphopoietic cell differentiation to the development and maintenance of epithelial cell adhesions. By recruiting histone-modifying enzymes to specific promoter sequences, MTA proteins can function both as transcriptional repressors and activators of a number of cancer-relevant proteins, including Snail, E-cadherin, signal transducer and activator of transcriptions (STATs), and the estrogen receptor. Their involvement in the epithelial-mesenchymal transition process and regulatory interactions with estrogen receptor activity has made MTA proteins highly interesting research candidates, especially in the field of hormone-sensitive breast cancer and malignancies of the female reproductive tract. This review focuses on the current knowledge about the function and regulation of MTA1 and MTA3 proteins in gynecological cancer, including ovarian, endometrial, and cervical tumors.

Wheat landraces are better qualified as potential gene pools at ultraspaced rather than densely grown conditions.

The negative relationship between the yield potential of a genotype and its competitive ability may constitute an obstacle to recognize outstanding genotypes within heterogeneous populations. This issue was investigated by growing six heterogeneous wheat landraces along with a pure-line commercial cultivar under both dense and widely spaced conditions. The performance of two landraces showed a perfect match to the above relationship. Although they lagged behind the cultivar by 64 and 38% at the dense stand, the reverse was true with spaced plants where they succeeded in out-yielding the cultivar by 58 and 73%, respectively. It was concluded that dense stand might undervalue a landrace as potential gene pool in order to apply single-plant selection targeting pure-line cultivars, attributable to inability of plants representing high yielding genotypes to exhibit their capacity due to competitive disadvantage. On the other side, the yield expression of individuals is optimized when density is low enough to preclude interplant competition. Therefore, the latter condition appears ideal to identify the most promising landrace for breeding and subsequently recognize the individuals representing the most outstanding genotypes.

Epigenetic silencing of the LDOC1 tumor suppressor gene in ovarian cancer cells.

PURPOSE: Due to very unspecific symptoms ovarian cancer often is diagnosed only at a late stage of the disease. Thus, morbidity and mortality of the patients are high. Even the established tumor marker CA12-5 shows only low specificity, rising the need for alternative biomarkers capable of detecting early stages of ovarian cancer. We analyzed the expression of the tumor suppressor candidate gene LDOC1 (leucine zipper downregulated in cancer 1) as a potential early biomarker in ovarian cancer cell lines. METHODS: A total of seven ovarian cancer cell lines were analyzed by RT-PCR (reverse transcriptase polymerase chain reaction) and real-time PCR for expression of LDOC1. Verification of promoter methylation was performed using methylation-specific primers on bisulfite-modified genomic DNA. RESULTS: Three out of seven ovarian cancer cell lines showed a complete loss of LDOC1 gene expression. LDOC1 silencing was caused neither by gene deletion nor gene rearrangements, but by methylation and subsequent inactivation of the concerned promoter as proofed by methylation specific primers. Similarly, promoter methylation could be inhibited by adding AdC (5-aza-2'-deoxycytidine), an inhibitor of DNA methyltransferases. As a result, a reactivation of the LDOC1 gene was seen. CONCLUSIONS: The tumor suppressor gene LDOC1 in ovarian cancer cell lines is downregulated by promoter methylation and thus may serve as an early biomarker. Further investigation will show if detection of methylated LDOC1 in peripheral blood has both adequate sensitivity and specificity for a timely non-invasive detection of ovarian cancer.