Progesterone Metabolism In Digitalis And Other Plants - 60 Years Research And Recent Results.

5ß-Cardenolides are pharmaceutically important metabolites of the specialized metabolism of Digitalis lanata. They were used over decades to treat cardiac insufficiency and supraventricular tachycardia. Since the 1960s, plant scientists have known that progesterone is an essential precursor of cardenolide formation. Therefore, plant progesterone biosynthesis was mainly analyzed in species of the cardenolide-containing genus Digitalis during the following decades. Today, Digitalis enzymes catalyzing the main steps of progesterone biosynthesis are known. Most of them were found in a broad range of organisms. This review will summarize the findings of 60 years of research on plant progesterone metabolism with a particular focus on the recent results in Digitalis lanata and other plants.

IGMPlot: A program to identify, characterize, and quantify molecular interactions.

We describe the development and features of a program called IGMPlot, which is based on the independent gradient model (IGM) and its local descriptor δ g . The IGM approach analyzes the gradient of the electron density (ED) in a molecular system to identify regions of space where chemical interactions take place. IGMPlot is intended for use by both experimental scientists and theoretical chemists. It is standalone software written in C++, with versions available for multiple platforms. Some key features are: probing and quantifying interactions between two given molecular fragments, determining bond strength (IBSI), estimating the atomic contributions to an intermolecular interaction and preparing data to build 2D and 3D representations of interaction regions. The software has been updated to include new features: critical point analysis of the ED, assessing ED asymmetry of a given bond (PDA) and a new descriptor called q g designed to enhance the IGM- δ g analysis. The program can be found at: http://igmplot.univ-reims.fr.

Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants.

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0-23+6 weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0-23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort. We also report a comparator population of 24+0-26+6 weeks gestation. All patients in the HS epoch were evaluated between 12-18h postnatal age and treated based on disease physiology whereas the HC patients underwent echocardiography at the discretion of the clinical team. We demonstrate a two-fold reduction in the composite primary outcome of death prior to 36 weeks or severe BPD and report a lower incidence of severe intraventricular hemorrhage (n=5, 7% vs n=27, 27%), necrotizing enterocolitis (n=1, 1% vs n=11, 11%) and first-week vasopressor use (n=7, 11% vs n=40, 39%) in the HS cohort. HS was also associated with an increase in survival free of severe morbidity from the already high rate of 50% to 73% among neonates <24 weeks gestation. We present a biophysiological rationale behind the potential modulator role of hsPDA on these outcomes and review the physiology relevant to neonates born at these extremely preterm gestations. These data highlight the need for further interrogation of the biological impact of hsPDA and impact of early echocardiography directed therapy in infants born less than 24 weeks gestation.

Characterization of the complete mitochondrial genomes of two Critically Endangered wedgefishes: Rhynchobatus djiddensis and Rhynchobatus australiae.

We present the complete mitochondrial genomes of the Critically Endangered whitespotted wedgefish, Rhynchobatus djiddensis (Forsskål, 1775), and bottlenose wedgefish, Rhynchobatus australiae (Whitley, 1939), with the R. djiddensis mitogenome documented for the first time. The genomes for R. djiddensis and R. australiae are 16,799 and 16,805 bp in length, respectively. Both comprise 13 protein-coding regions, 22 tRNA genes, two rRNA genes, and a non-coding control region. All protein-coding regions consistently start with the ATG start codon; however, the alternative start codon GTG is observed at the start of the COX1 gene. NADH2, COX2, and NADH4 have incomplete stop codons: T or TA, and tRNALeu and tRNASer , have atypical codons: UAA, UGA, GCU, and UAG. The phylogenetic analysis places R. djiddensis and R. australiae within the Rhynchobatus genus, separate from other families in the order Rhinopristiformes. We also highlight the most variable gene regions to expedite future primer design, of which NADH2 was the most variable (4.5%) when taking gene length into account. These molecular resources could promote the taxonomic resolution of the whitespotted wedgefish species complex and aid in the genetic characterization of populations of these and related species.

[Processing of medical products in the urological practice]. / Aufbereitung von Medizinprodukten in der urologischen Praxis.

The reprocessing of medical products is an important topic both in urological practices and in hospitals. The complexity is caused by the increasing variety of medical instruments and also by the increasing demands on the legally required quality of the reprocessing. The Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM) have published recommendations for the processing of MD and last updated them in 2012. This article summarizes the legal framework for the reprocessing of medical devices, how medical devices are categorized before the appropriate procedure for reprocessing can be selected and the various steps in the reprocessing. A special focus is placed on medical products that are typically found in urological practices or outpatient departments and are processed there. Furthermore, the necessity of validating the processing method and the required training (expertise) of the personnel are discussed.

Control of structure and spin texture in the van der Waals layered magnet CrSBr.

Controlling magnetism at nanometer length scales is essential for realizing high-performance spintronic, magneto-electric and topological devices and creating on-demand spin Hamiltonians probing fundamental concepts in physics. Van der Waals (vdW)-bonded layered magnets offer exceptional opportunities for such spin texture engineering. Here, we demonstrate nanoscale structural control in the layered magnet CrSBr with the potential to create spin patterns without the environmental sensitivity that has hindered such manipulations in other vdW magnets. We drive a local phase transformation using an electron beam that moves atoms and exchanges bond directions, effectively creating regions that have vertical vdW layers embedded within the initial horizontally vdW bonded exfoliated flakes. We calculate that the newly formed two-dimensional structure is ferromagnetically ordered in-plane with an energy gap in the visible spectrum, and weak antiferromagnetism between the planes, suggesting possibilities for creating spin textures and quantum magnetic phases.

Benign stenosis of common bile duct after Roux Y gastrectomy.

We present the case of a 60-year-old patient with the history of subtotal gastric resection and reconstruction of passage using the Roux-Y loop, five years later diagnosed with benign stenosis of the common bile duct. The possibilities of using endoscopy and interventional radiology for the bile duct treatment in the postoperatively altered terrain of the proximal digestive tract were limited. After failure of these methods the patient was indicated for surgery - biliodigestive anastomosis. The postoperative course was significantly complicated by bleeding and formation of bile and colic fistulas. Over time, a migrated stent was found in the small intestine, which was the cause of inflammatory changes and incomplete small bowel obstruction. Increased intraluminal pressure in the intestinal loops inhibited healing of the anastomosis and was a major cause of the complications.

Development and psychometric properties of a brief generic cancer knowledge scale for patients (BCKS-10).

PURPOSE: This study aims to introduce the development and psychometric properties of a brief generic cancer knowledge scale for patients (BCKS-10) that includes different elements of knowledge and skills (terminology, diagnosis, treatment, prevention, and numeracy). Although cancer knowledge is a central dimension of cancer literacy, most previous studies either investigated cancer knowledge among the general population, or among patients with a specific cancer diagnosis. METHODS: Qualitative interviews (n = 11) and a quantitative survey (n = 267) among peer support group leaders were conducted to further develop the BCKS-10 after literature screening. n = 500 patients with cancer were recruited across Germany between October 2020 and February 2021. Construct validity, item discrimination and reliability were tested. RESULTS: ANOVA revealed no significant differences of the knowledge score between various cancer sites, a significant positive association with education, and a negative association with migration background by trend supporting construct validity. In terms of item discrimination, the corrected item-total correlation of 8 out of 10 items were above the threshold of 0.3. Cronbach's alpha of about 0.68 revealed an acceptable internal consistency as the tool is brief and consists of different dimensions. CONCLUSION: Overall, the findings show that the BCKS-10 is a suitable tool to briefly assess cancer knowledge among patients independent of cancer site. However, further surveys have to be conducted to validate the psychometric properties and enhance the BCKS-10.

Whole exome sequencing of known eye genes reveals genetic causes for high myopia.

High myopia [refractive error ≤ -6 diopters (D)] is a heterogeneous condition, and without clear accompanying features, it can be difficult to pinpoint a genetic cause. This observational study aimed to evaluate the utility of whole exome sequencing (WES) using an eye disorder gene panel in European patients with high myopia. Patients with high myopia were recruited by ophthalmologists and clinical geneticists. Clinical features were categorized into isolated high myopia, high myopia with other ocular involvement or with systemic involvement. WES was performed and an eye disorder gene panel of ~500 genes was evaluated. Hundred and thirteen patients with high myopia [mean (SD) refractive error - 11.8D (5.2)] were included. Of these, 53% were children younger than 12 years of age (53%), 13.3% were aged 12-18 years and 34% were adults (aged > 18 years). Twenty-three out of 113 patients (20%) received a genetic diagnosis of which 11 patients displayed additional ocular or systemic involvement. Pathogenic variants were identified in retinal dystrophy genes (e.g. GUCY2D and CACNA1F), connective tissue disease genes (e.g. COL18A1 and COL2A1), non-syndromic high myopia genes (ARR3), ocular development genes (e.g. PAX6) and other genes (ASPH and CNNM4). In 20% of our high myopic study population, WES using an eye gene panel enabled us to diagnose the genetic cause for this disorder. Eye genes known to cause retinal dystrophy, developmental or syndromic disorders can cause high myopia without apparent clinical features of other pathology.

[Safety and efficacy of en bloc vs. conventional transurethral resection of bladder tumors: a meta-analysis and systematic review]. / Sicherheit und Effizienz der en bloc vs. konventionellen transurethralen Resektion von Blasentumoren: eine Metaanalyse und systematic Review.

BACKGROUND: En bloc tumor resection of bladder tumors (ERBT) is a novel alternative procedure to conventional resection of bladder tumor (cTURBT), which might help to address common problems of the standard method, such as inadequate detrusor muscle in specimens, high re-resection rates and high recurrence rates. OBJECTIVE: To analyze current data on ERBT in efficacy and safety compared to cTURBT. DATA SOURCES: PubMed. STUDY SELECTION: Two independent authors identified trials based on keywords and inclusion criteria. A third author was consulted in case of discrepancies. Screening keywords: ERBT, en bloc transurethral resection of bladder tumor, TURBT en bloc. A meta-analysis of 13 studies was performed. The effect size was estimated based on odds ratios and mean differences including their corresponding two-sided 95% confidence intervals. DATA SYNTHESIS: The analyzed studies comprised a homogenous collective in terms of tumor size, tumor multiplicity and tumor stage. Operation time did not significantly differ between the methods. Differences were observed in hospitalization and catheterization time in favor of ERBT. Reported complications did not show clear differences. There was significantly more detrusor muscle in the specimens in the ERBT group. No significant differences were found in recurrence up to 2 years of follow-up. CONCLUSION: ERBT is a safe alternative to conventional TURBT with promising features regarding effective resection of detrusor muscle. More standardized data on recurrence rates, different resection modalities and resection margin results are needed.

Hypertension-mediated organ damage in masked hypertension.

OBJECTIVES: Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring. METHODS: Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg). Evidence of hypertension-mediated organ damage was compared in patients with sustained normotension, masked hypertension, and sustained hypertension based on measurements by HBPM, daytime ABPM, and 24-h ABPM. RESULTS: The 420 participants averaged 48 (12) [mean (SD)] years of age; the average clinic BP was 130 (13)/81 (8) mmHg. In individuals with masked hypertension diagnosed by HBPM, indexed LV mass, relative wall thickness, and e' and E/e' (indices of LV relaxation), were generally intermediate between values observed in normotensives and sustained hypertensive patients, and were significantly greater in masked hypertension than normotensives. Similar trends were observed when masked hypertension was diagnosed by ABPM but a diagnosis of masked hypertension was not as reliably associated with LV remodeling or impaired LV relaxation in comparison to normotensives. There were trends towards greater likelihoods of detectable urinary microalbumin and coronary calcification in masked hypertension than in normotensives. CONCLUSION: These results support previous studies demonstrating early hypertension-mediated organ damage in patients with masked hypertension, and suggest that HBPM may be superior to ABPM in identifying patients with masked hypertension who have early LV remodeling and diastolic LV dysfunction.

Coronary Artery Calcifications and Cardiac Risk After Radiation Therapy for Stage III Lung Cancer.

PURPOSE: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. METHODS AND MATERIALS: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. RESULTS: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. CONCLUSIONS: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.

Synchronous tumor duplicity of a neuroendocrine tumor of Meckels diverticulum with liver metastases and colorectal carcinoma.

INTRODUCTION: Meckels diverticulum (MD) is a developmental abnormality and a true diverticulum of the small intestine which can give rise to a malignant tumor. Neuroendocrine tumors (NETs) are the most common tumors arising in MD, but due to the prevalence of MD and its malignancy rate, there is no uniform guideline regarding these tumors. Recent knowledge shows that their biological behavior is aggressive and unrelated to size. Their behavior resembles that of an ileal NET. CASE REPORT: A 62-year-old male was examined for enterorrhagia, and an adenocarcinoma of the ascending colon was diagnosed along with multiple liver lesions that resembled metastases. Needle biopsy of a liver lesion was performed and showed the lesions to be NET metastases of unknown origin. Treatment with somatostatin analogs was commenced, and because of the patients anemization a right hemicolectomy was indicated, during which a normal Meckels diverticulum was found and resected. Histological evaluation of MD confirmed a moderately differentiated NET. CONCLUSION: Surgery is the primary modality for treating MD, including cases in which MD is asymptomatic and found incidentally during surgery for other causes. In the case of NET of MD, a radical surgical treatment is needed because of the risk of early metastatic dissemination. When liver metastases are present, an aggressive approach combining surgical and systemic treatment is recommended to improve the prognosis of the disease.

LC3A positive "stone like structures" are differentially associated with survival outcomes and CD68 macrophage infiltration in patients with lung adenocarcinoma and squamous cell carcinoma.

AIMS: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression. METHODS: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides. RESULTS: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC. CONCLUSIONS: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.

Productive performance of beef cows subjected to different nutritional levels in the third trimester of gestation.

In general, calf production occurs in less intensive systems. The limitation of nutrients during the gestation phase of beef cows can have negative impacts on the consequent productivity of females. Therefore, this study aimed to evaluate the effects of nutritional levels in the third trimester of pregnancy on the productive performance of beef cows kept in a natural pasture (NP). Eighty-three Charolais × Nelore cows were used, ranging in age from 4 to 12 years, which were divided according to their nutritional levels during the third trimester of pregnancy: NP, cows supplemented with 100% of their energy and protein requirements (SP100) and cows supplemented with 150% of their energy and protein requirements (SP150). The experimental design was completely randomized with three treatments and a varied number of repetitions. The SP100 and SP150 cows presented better body condition at calving (2.92 and 2.99 vs 2.81 points) and at the start of the breeding season (2.90 and 2.95 vs 2.80 points) than did NP cows. The nutritional level of the cows in the third trimester of gestation did not influence the blood metabolite concentrations. The plasma levels of albumin and total proteins were 3.11 and 8.18 g/dl, respectively. Glucose and cholesterol showed values of 74.96 and 166.50 mg/dl. The lowest concentration of blood metabolites was observed in the first postpartum weeks. The SP100 and SP150 cows showed faster follicular growth and, consequently, a higher percentage of females with ovulatory follicles at 21 days postpartum than did NP cows (45.68, 41.11, and 11.00%, respectively). The SP150 cows had a higher pregnancy rate (40.74%), total calf production (295.88 kg/cow), and consequently, offspring sale value. An increased nutritional level in the third trimester of pregnancy improves the postpartum metabolic condition and productive efficiency of beef cows kept on NP.

Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Performance of faecal indicator bacteria, microbial source tracking, and pollution risk mapping in tropical water.

Faecal indicator bacteria (FIB) are used for the assessment of faecal pollution and possible water quality deterioration. There is growing evidence that FIB used in temperate regions are not adequate and reliable to detect faecal pollution in tropical regions. Hence, this study evaluated the adequacy of FIB, including total coliforms (TC), Escherichia coli (EC), Enterococci (IEC), and Clostridium perfringens (CP) in the high-altitude, tropical country of Ethiopia. In addition to FIB, for microbial source tracking (MST), a ruminant-associated molecular marker was applied at different water types and altitudes, and faecal pollution risk mapping was conducted based on consensus FIB. The performances of the indicators were evaluated at 22 sites from different water types. The results indicate that EC cell enumeration and CP spore determination perform well for faecal contamination monitoring. Most of the sub-basins of Lake Tana were found to be moderately to highly polluted, and the levels of pollution were demonstrated to be higher in the rainy season than in the post-rainy season. Markers associated with ruminants (BacR) were identified in more than three quarters of the sites. A bacterial pollution risk map was developed for sub-basins of Lake Tana, including the un-gauged sub-basins. We demonstrate how bacterial pollution risk mapping can aid in improvements to water quality testing and reduce risk to the general population from stream bacteria.

Conditional Survival in Uveal Melanoma.

PURPOSE: To investigate conditional survival in patients with uveal melanoma in the United States. DESIGN: Cohort study. PARTICIPANTS: Patients were identified using International Classification of Disease for Oncology, Third Edition, codes for both morphologic features (melanoma, 8720-8790) and site (retina, C69.2; choroid, C69.3; and ciliary body, C69.4) from 1975 through 2011 using the Surveillance, Epidemiology, and End Results (SEER) database SEER 18. METHODS: Observed metastasis-free survival (MFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Conditional metastasis-free survival (cMFS) and conditional overall survival were calculated based on the observed MFS and OS. Relative survival also was calculated using the actuarial method. Survival to 5 and 10 years after diagnosis were calculated, conditioned on various numbers of years already survived. MAIN OUTCOME MEASURES: Conditional MFS, conditional OS, and conditional relative survival. RESULTS: A total of 6863 cases of uveal melanoma were identified. Median follow-up among survivors was 11 years. During follow-up, 3883 patients died of any cause, and of these, 2131 deaths were the result of metastatic uveal melanoma. The nonconditional 5-year MFS was 80%. After surviving 1, 2, 3, or 4 years after diagnosis, the 5-year cMFS estimates increased to 82%, 87%, 92%, and 96%, respectively. The nonconditional MFS at 10 years was estimated to be 69%. After having survived 5, 6, 7, 8, or 9 years after diagnosis, the 10-year cMFS estimates increased to 87%, 90%, 93%, 96%, and 98%, respectively. This result pattern was confirmed with estimates of relative survival. CONCLUSIONS: Conditional survival estimates of uveal melanoma improve with time since primary diagnosis. Among patients who already have survived for at least 5 years, 10-year conditional survival rates are high. Conditional survival analysis can provide specific guidance for counselling patients.

Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Württemberg, Germany.

We investigated data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected 0-19 year olds, who attended schools/childcare facilities, to assess their role in SARS-CoV-2 transmission after these establishments' reopening in May 2020 in Baden-Württemberg, Germany. Child-to-child transmission in schools/childcare facilities appeared very uncommon. We anticipate that, with face mask use and frequent ventilation of rooms, transmission rates in schools/childcare facilities would remain low in the next term, even if classes' group sizes were increased.