A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX).

OBJECTIVE: Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy. MATERIALS AND METHODS: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 (<2 cm for fertility sparing), with negative LN on pre-operative imaging. Intra-operatively, patients are excluded when there is a failure to detect SLN on both sides of the pelvis in cases of more advanced cancer (stage >IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up. CONCLUSIONS: The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063).

Rationale for routine collection of patient reported outcomes during integrative medicine consultation visits.

OBJECTIVES: Integrative medicine (IM) is whole-person care utilizing complementary health approaches to address numerous physical or emotional influences that can impact an individual's health. Patient-reported outcomes (PRO) are subjective measures that quantify patients' perception of their quality of life. While PRO measures have been routinely assessed in specific oncology clinics, our objective was to assess the ability and utility of routine collection of PRO measures in an IM clinic. DESIGN/SETTING/MAIN OUTCOME: Patients receiving a clinical consultation in an ambulatory IM clinic completed the PROMIS Global Health Form in the clinic waiting room. RESULTS: From November 2013 through October 2016, the PROMIS Global Health Form (PROMIS-10) was administered during 59% of IM provider consultation visits (7172/12,207), representing 3473 unique patients. Most patients were female (81%), White (93%), middle-aged (49.2; SD 15.4) and had commercial health insurance (66%). Baseline Mental (44.9; SD 9.1) and Physical Health (44.2; SD 8.6) scores were roughly 0.5 standard deviation below the national mean values (50; SD 10). Factors such as age, race and non-commercial insurance were associated with lower PROMIS-10 scores. Patients completing at least two PROMIS-10 questionnaires (n = 1541) exhibited increases of 2.3% and 2.8% from first to last PROMIS-10 assessment in Mental and Physical Heath scores respectively. CONCLUSIONS: It is possible to routinely collect PRO measures in large IM clinic and longitudinal improvements in Mental and Physical Health scores were observed. Future research should focus on understanding how providers can utilize PRO results in real-time to improve patients' clinical outcomes and potentially decrease healthcare utilization.

Acid rain footprint three decades after peak deposition: Long-term recovery from pollutant sulphate in the Uhlirska catchment (Czech Republic).

The granitic Uhlirska headwater catchment with a size of 1.78km2 is located in the Jizera Mountains in the northern Czech Republic and received among the highest inputs of anthropogenic acid depositions in Europe. An analysis of sulphate (SO42-) distribution in deposition, soil water, stream water and groundwater compartments allowed to establish a SO42- mass-balance (deposition input minus surface water export) and helped to evaluate which changes occurred since the last evaluation of the catchment in 1997. The determined SO42- concentrations decreased in the following order: wetland groundwater>groundwater from 20m below ground level (bgl)>groundwater from 30m bgl>stream water>groundwater from10m bgl>hillslope soil water>wetland soil water>bulk deposition with median values of 0.24, 0.21, 0.17, 0.15, 0.11, 0.07, 0.03 and 0.01mmolL-1, respectively. Our results show that average deposition reductions of 62% did not result in equal changes of the sulphate mass-balance, which changed by only 47%. This difference occurs because sulphate originates from internal sources such as the groundwater and soil water. The Uhlirska catchment is subject to delayed recovery from anthropogenic acid depositions and remains a net source of stored sulphur even after three decades of declining inputs. The wetland groundwater and soil water provide environmental memories of legacy pollutant sulphate. Elevated stream water sulphate concentrations after the unusually dry summer 2015 imply importance of weather and climate patterns for future recovery from acidification.

[Long-term functional effect of the photo screening in ocular diseases causing amblyopia]. / Dlouhodobýy funkcní efekt fotoscreeningu amblyogenních ocních vad.

Amblyopia represents the most common cause of insufficient monocular visual acuity in productive age.To begin the treatment in the early childhood is understood as the fundamental anticipation to achieve the optimal result. The research work concerns about the development of screening methods. Our retrospective study was not focused toward the efficacy of the screening itself, but it had to establish, how the participation of the suckling babies in the screening program influences the chance of good vision. The data analyzed in this study were obtained from retrospective review of medical records of two groups of patients of the Center for functional visual disorders. Four hundred and nineteen (419) patients with positive finding in the photo screening, selected by chance, were included into the study (SC group). In the second group, there were included 263 randomly selected patients who did not pass the photo screening procedure and to the first examination were referred by the pediatrician (PLDD group).The average age at the time of the first examination was 13 months in children from the SC group and 23 months in children from the PLDD group respectively.The difference was statistically highly significant. In both groups, the severity of the amblyopia related to the comparable degree of anisometropia and the degree of the involvement of binocular functions in strabismus related to the comparable degree of hypemetropia were compared. The data were evaluated according to the age of the child patients at the time of the examination used for the purpose of this study as well. The obtained data show, that the decrease of the visual acuity of the amblyopic eye in case of equal anisometropia is significantly higher in two to three years old children who were not screened. In older children, the results in the in the SC and PLDD groups did not significantly differ. The results of our study indicate that later (before the age of three years) beginning of systematic pleoptic treatment related to the absence in the screening program is not worsening the chance to good visual acuity at the age of six years in case of moderate to mid-severe amblyopia. The first examination indicated by the pediatrician later, at the time of evident signs of strabismus, may decrease the chance to the good functional results of the complex strabological treatment at the age of six years.

Time-course of tissue factor plasma level in patients with acute coronary syndrome.

Enhanced expression of tissue factor (TF) may result in thrombosis contributing to acute clinical consequences of coronary artery disease. Several studies demonstrated elevated plasma levels of TF in patients with acute coronary syndrome (ACS). The aim of our study was to compare the concentrations of TF in coronary sinus (CS), proximal part of the left coronary artery (LCA) and peripheral vein (PV) of patients with ACS and stable coronary artery disease (SCAD). Time course of the TF plasma levels in PV was followed on day 1 and day 7 after index event of ACS presentation and was compared to day 0 values. No heparin was given prior to the blood sampling. Twenty-nine patients in the ACS group (age 63.6+/-10.8 years, 20 males, 9 females) and 24 patients with SCAD (age 62.3+/-8.1 years, 21 males, 3 females) were examined. TF plasma level was significantly higher in patients with ACS than in those with SCAD (239.0+/-99.3 ng/ml vs. 164.3+/-114.2 ng/ml; p=0.016). There was no difference in TF plasma levels in PV, CS and LCA (239.0+/-99.3 ng/ml vs. 253.7+/-131.5 ng/ml vs. 250.6+/-116.4 ng/ml, respectively). TF plasma levels tended to decrease only non-significantly on the day 7 (224.4+/-109.8 ng/ml). Significant linear correlation between TF and high sensitivity CRP (hs-CRP) levels on day 0 was found. In conclusion, TF plasma levels are elevated in patients with ACS not only locally in CS but also in systematic circulation. Our data support the relationship between TF production and proinflammatory mediators.

Biotic elicitation of the Trifolium pratense L. suspension culture.

The important substances of secondary metabolism include flavonoids and isoflavonoids. The Trifolium pratense L. (Fabaceae) suspension culture's yield of these metabolites is low, thus an attempt was made to increase the production by elicitation. The endogenous signal substances of the plants' defensive responses include jasmonic acid that also functions as a biotic elicitor in the case of exogenous application. In the experiment the authors monitored the impact of 4 different concentrations of jasmonic acid on the Trifolium pratense L. (variety DO-8 and variety DO-9) suspension culture's yield. The culture was cultivated in Gamborg medium to which 2 mg.l(-1) of 2,4-dichlorophenoxyacetic acid and 2 mg.l(-1) of 6-benzylaminopurine were added. The maximum increase in the production of flavonoids was achieved, when compared with the control samples, with both varieties of the 500 micromol concentration (DO-9, 6-hour application by 140%; DO-8, 24-hour application by 65%). The production of isoflavonoids (genistin, daidzein, genistein, and formononetine) was best stimulated in both varieties by the 50 micromol concentration (in the case of DO-9 variety, the 48-hour application increased the content of genistin by up to 845%).

Effects of Mg-ATP on the flavonoid production in the Scutellaria baicalensis Georgii suspension cultures.

This work focused on the cultivation of S. baicalensis Georgii in vitro cultures and on the possibilities of increasing the production of secondary metabolites in these cultures. The aim of the Sstudy was to determine whether the baicalin transport through vacuolar membrane is dependent on the presence of Mg-ATP. Our results showed that Mg-ATP had a significant effect on the ratio of baicalin and baicalein content and on the transport speed of these flavonoids. Therefore, the transport mechanism for baicalin are probably some of the MRP proteins which are the subfamily of the ABC transporte

Plasma tissue factor in coronary artery disease: further step to the understanding of the basic mechanisms of coronary artery thrombosis.

Tissue factor is a cell surface protein that is expressed constitutively by monocytes, macrophages and fibroblasts, but also by some other cells in response to a variety of stimuli. The main function of the tissue factor is to form a complex with factor VII/VIIa that converts factors IX and X to their active forms. Tissue factor is also involved in the pathophysiology of systemic inflammatory disorders, coagulopathies, atherosclerotic disease, tumor angiogenesis and metastasis. Increased tissue factor expression either locally in the coronary plaques or systematically on circulating blood elements of patients with acute coronary syndromes may be responsible for increased thrombin generation, thus leading to platelet activation and fibrin formation. Tissue factor therefore plays a pivotal role in the initiation of thrombotic complications in patients with coronary artery disease.

Abiotic elicitation of Trifolium pratense L. suspension culture.

Important substances of secondary metabolism include flavonoids and isoflavonoids. The Trifolium pratense L. (Fabacae) suspension culture is characterized by low production of these metabolites and therefore we tried to influence the production output with elicitation. From their origin point of view, the elicitors are divided into two groups - biotic and abiotic. The latter group includes, for instance, the salts of heavy metals. Our work was aimed at observing the effect of the copper sulphate abiotic elicitor on the production of the Trifolium pratense L. suspension culture (variety DO-8 and variety DO-9) that was cultivated in Gamborg media supplemented with 2 mg l(-1) of 2,4-dichlorophenoxyacetic acid and 2 mg l(-1) of 6-benzylaminopurine. The maximum increase in the flavonoid production took place, when compared with the test check, during the 168-hour application of the 100 micromol concentration. The DO-8 variety isoflavonoids production was stimulated namely during the 48-hour application of the I micromol concentration; the best elicitation effect of the DO-9 variety was achieved with the 168-hour application of the 10 micromol concentration.

Reduction of proteinuria during intensified antihypertensive therapy in children after renal transplantation.

BACKGROUND: Proteinuria together with hypertension are known risk factors for poor allograft as well as patient survivals after renal transplantation. In adults, proteinuria can be reduced by lowering blood pressure and by using angiotensin-converting enzyme inhibitors. In children, no study has investigated the antiproteinuric effects of antihypertensive therapy. Herein we investigated changes in proteinuria among a subgroup of children with proteinuria>or=200 mg/m2d in an interventional study primary aimed to improve the efficacy of antihypertensive therapy. PATIENTS AND METHODS: Twelve children with proteinuria>or=200 mg/m2d were included in the study. Proteinuria was investigated at baseline and at 1 year after changes in antihypertensive therapy. Blood pressure (BP) was measured using ambulatory BP monitoring. RESULTS: The median protein excretion of 226 mg/m2/d (range, 41-1478 mg/m2/d) at 1 year before the study did not change significantly at study baseline (278 mg/m2/d; range, 205-1264 mg/m2/d), but decreased significantly to 199 mg/m2/d (range, 65-749 mg/m2/d) after 1 year (P<.05 vs baseline). The number of antihypertensive drugs was increased from 1.6+/-1.0 to 2.2+/-0.9 drugs/patient after 1 year (P<.05). The use of different classes of antihypertensive drugs did not change significantly. Mean ambulatory systolic and diastolic BP at daytime and diastolic BP at nighttime did not change significantly after 1 year; mean ambulatory systolic BP at night decreased from 1.60+/-1.54 to 1.04+/-0.97 standard deviation score (P<.05). Graft function did not change significantly. CONCLUSION: We demonstrated that proteinuria among children after renal transplantation was reduced by intensified antihypertensive therapy using all classes of antihypertensive drugs.

Fagopyrum esculentum in vitro.

Common buckwheat is a valuable source of the flavonoid rutin. Its in vitro culture was derived from a young seedling plant and the content of flavonoids in the callus culture was compared with their content in an intact plant. The optimal nutrient medium for the cultivation of the in vitro culture and for the production of flavonoids is Murashige and Skoog medium which contains, during the cultivation in the normal light regime, the growth regulators combination of 2,4-D 1 mg/l and kinetin 1 mg/l.

[Genista tinctoria in vitro]. / Genista tinctoria in vitro.

The paper deals with the effects of different growth regulators on the growth of the culture and production of isoflavonoids in the cultivation of the callus culture Genista tinctoria on MS medium under varying light regimens. Of the regulators tested, the highest growth of the culture was found when using BAP 10 mg/l under continuous lighting. With the use of BAP 0.1 mg/l and under normal light regimen, the production of genistine and daidzenin was even higher than in the intact plant. Of the five isoflavonoids determined, four were demonstrated in the callus culture: genistine, genistein, daidzein, and formononetin. In the intact plant the authors managed to determine daidzein, genistein, and biochanin A.

Flavonoid accumulation in Scutellaria baicalensis Georgii in vitro cultures upon treatment with sodium cinnamate.

The production of secondary metabolites by plant cell cultures has been suggested as a feasible technology that attracted considerable industrial and academic interest in the past three decades. However, many secondary pathways are not well expressed in plant cell cultures. Optimization of culture medium, elicitation, genetic engineering and the supply of biosynthetic precursors are among the strategies adopted to increase secondary metabolite production in vitro. In this study, the effects of five potential biosynthetic precursors on the production of baicalin and baicalein in Scutellaria baicalensis Georgii suspension and callus cultures were measured. The results of this work show that flavonoid biosynthesis was most stimulated by the addition of sodium cinnamate in the concentration of 5 mg x l(-1) and by cinnamic acid (1 mg x l(-1)). Feeding with L-phenylalanine, malonic acid and sodium malonate did not induce changes in the amounts of flavonoids, and the biomass production was not affected.

CIRCADIAN BLOOD PRESSURE VARIABILITY AND EXERCISE THERAPY.

The objective of this study was to find if there was a relationship between the time when cardiovascular rehabilitation was running in the patients after myocardial infarction and an average daily value of systolic and diastolic blood pressure at 7-day ambulatory blood pressure monitoring.Systolic and diastolic pressures significantly increased in patients who underwent cardiovascular rehabilitation in the morning from 9.00 a.m. to 10.15 a.m., and significantly decreased in those who did their physical exercise in the afternoon from 1.30 p.m. to 2.45 p.m., compared to their blood pressure values on days without rehabilitation.

THE RELATIONSHIP BETWEEN CIRCADIAN BLOOD PRESSURE VARIATION AND AGE ANALYSED FROM 7-DAY MONITORING.

The relationship between age and circadian blood pressure (BP) variation was the aim of the present study. One hundred and eighty-seven subjects (130 males, 57 females), 20-77 years old, were recruited for seven-day BP monitoring. Colin medical instruments (Komaki, Japan) were used for ambulatory BP monitoring (oscillation method, 30-minute interval between measurements). A sinusoidal curve was fitted (minimum square method) and the mean value and amplitude of the curve (double amplitude corresponds to the night-day difference) were evaluated on every day of monitoring. The average 7-day values of the mean (M) and of double amplitude (2A) for systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were determined in each subject. The mean values of M (+/-SD) for the whole group were: SBP- 127+/-8, DBP - 79+/-6 mmHg, HR - 70+/-6 bpm; of 2A: SBP - 21+/-7, DBP - 15+/-5 mmHg, HR - 15+/-6 bpm. A linear relationship between M of SBP and age (r=0.341, p< 0.001) and DBP and age (r=0.384, p<0.001) was found (difference between 20 and 77 years: SBP - 16, DBP - 12 mmHg). 2A of SBP and DBP was increasing with age up to 35 years, then the curve remained relatively flat up to 55 years (maximum at 45 years), and then it decreased again (difference between 45 and 77 years: SBP - 13mmHg, DBP - 12 mmHg). Heart rate M and 2A were age-independent. The mean values of SBP and DBP were increasing with age up to 75 years, but the night-day difference of SBP and DBP reached its maximum value at 45 years and then decreased.

CHRONOMICS AND GENETICS.

The mapping of time structures, chronomes, constitutes an endeavor spawned by chronobiology: chronomics. This cartography in time shows signatures on the surface of the earth, cycles, also accumulating in life on the earth's surface. We append a glossary of these and other cycles, the names being coined in the light of approximate cycle length. These findings are transdisciplinary, in view of their broad representation and critical importance in the biosphere. Suggestions of mechanisms are derived from an analytical statistical documentation of characteristics with superposed epochs and superposed cycles and other "remove-and-replace" approaches. These approaches use the spontaneously changing presence or absence of an environmental, cyclic or other factor for the study of any corresponding changes in the biosphere. We illustrate the indispensability of the mapping of rhythm characteristics in broader structures, chronomes, along several or all available different time scales. We present results from a cooperative cartography of about 10, about 20, and about 50-year rhythms in the context of a broad endeavor concerned with the Biosphere and the Cosmos, the BIOCOS project. The participants in this project are our co-authors worldwide, beyond Brno and Minneapolis; the studies of human blood pressure and heart rate around the clock and along the week may provide the evidence for those influences that Mendel sought in meteorology and climatology.

CHRONOBIOLOGY OF HIGH BLOOD PRESSURE.

BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health.Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms.New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs.

[Improved control of hypertension and its effect on graft function in children after renal transplantation]. / Zlepsená kontrola hypertenze a její vliv na funkci stepu u detí po transplantaci ledviny.

BACKGROUND: Hypertension in patients after renal transplantation (RTx) is associated with impaired graft functions and graft survival. Control of hypertension in children after RTx is low--only 20-50 % of children have well controlled hypertension. The aim of this interventional study is to improve blood pressure control and to investigate whether the improved control will improve the graft survival. METHODS AND RESULTS: 36 children after RTx (mean age 13.9 +/- 4.4 years, time after RTx 2.7 +/- 2.4) fulfilled the inclusion criteria. Ambulatory blood pressure monitoring (ABPM) and graft function were examined. In children with uncontrolled hypertension, the dose and number of antihypertensive drugs were increased to reach BP <95th centile. ABPM was repeated after 12 months. After 12 months day-time and night-time BP dropped non-significantly, however prevalence of uncontrolled hypertension improved significantly from 42 % to 34 % (p<0.05). Number of antihypertensive drugs increased from 2.1 +/- 0.9 to 2.4 +/- 0.8 drugs per patient (p<0.05), namely that of ACE-inhibitors (from 19% to 27%, p<0.05). Graft function decreased by 3.6 ml/min/1.73m2/year (p<0.05). CONCLUSIONS: This 12 months interventional trial demonstrated that control of hypertension in children after RTx can be improved by increasing number of prescribed antihypertensive drugs. The decline of graft function was lower comparing with previous trials.