Thermodynamic Bounds on Symmetry Breaking in Linear and Catalytic Biochemical Systems.

Living systems are maintained out of equilibrium by external driving forces. At stationarity, they exhibit emergent selection phenomena that break equilibrium symmetries and originate from the expansion of the accessible chemical space due to nonequilibrium conditions. Here, we use the matrix-tree theorem to derive upper and lower thermodynamic bounds on these symmetry-breaking features in linear and catalytic biochemical systems. Our bounds are independent of the kinetics and hold for both closed and open reaction networks. We also extend our results to master equations in the chemical space. Using our framework, we recover the thermodynamic constraints in kinetic proofreading. Finally, we show that the contrast of reaction-diffusion patterns can be bounded only by the nonequilibrium driving force. Our results provide a general framework for understanding the role of nonequilibrium conditions in shaping the steady-state properties of biochemical systems.

Antiphospholipid antibodies in patients with myocardial infarction with and without obstructive coronary arteries.

BACKGROUND: Recent studies demonstrate that prothrombotic antiphospholipid antibodies (aPL) are overrepresented in patients with myocardial infarction (MI) due to coronary artery disease (MICAD). However, it is not known whether aPL differ between the two subsets of MI: MICAD and MI with nonobstructive coronary arteries (MINOCA). OBJECTIVES: To determine whether aPL are associated with MINOCA or MICAD, or with hypercoagulability as assessed by activated protein C-protein C inhibitor (APC-PCI) complex. METHODS: Well-characterized patients with MINOCA (n = 98), age- and gender-matched patients with MICAD (n = 99), and healthy controls (n = 100) were included in a cross-sectional case-control study. Autoantibodies (IgA/G/M) targeting cardiolipin and ß2 glycoprotein-I and specific nuclear antigens were analyzed by multiplexed bead technology. The concentration of APC-PCI was determined as a measure of hypercoagulability by an immunofluorometric sandwich assay. RESULTS: Both prevalence and titers of aPL of the IgG isotype (anti-cardiolipin and/or anti-ß2 glycoprotein-I) were higher in patients with MINOCA and MICAD than in controls. aPL IgG positivity was twice as frequent among patients with MICAD than MINOCA (11% vs. 6%, nonsignificant). We observed no group differences regarding aPL IgA/M or antibodies targeting specific nuclear antigens. Levels of APC-PCI were elevated in aPL IgG-positive compared to aPL IgG-negative MICAD patients. CONCLUSIONS: aPL IgG, but not IgA/M, are enriched particularly in patients with MICAD but also in patients with MINOCA, as compared to controls. Interestingly, signs of hypercoagulability-measured by increased levels of the APC-PCI complex-were present in aPL IgG-positive MICAD patients, indicating an association with functional disturbances of the coagulation system.

Mutual Information Disentangles Interactions from Changing Environments.

Real-world systems are characterized by complex interactions of their internal degrees of freedom, while living in ever-changing environments whose net effect is to act as additional couplings. Here, we introduce a paradigmatic interacting model in a switching, but unobserved, environment. We show that the limiting properties of the mutual information of the system allow for a disentangling of these two sources of couplings. Further, our approach might stand as a general method to discriminate complex internal interactions from equally complex changing environments.

Dissipation-Driven Selection under Finite Diffusion: Hints from Equilibrium and Separation of Time Scales.

When exposed to a thermal gradient, reaction networks can convert thermal energy into the chemical selection of states that would be unfavourable at equilibrium. The kinetics of reaction paths, and thus how fast they dissipate available energy, might be dominant in dictating the stationary populations of all chemical states out of equilibrium. This phenomenology has been theoretically explored mainly in the infinite diffusion limit. Here, we show that the regime in which the diffusion rate is finite, and also slower than some chemical reactions, might bring about interesting features, such as the maximisation of selection or the switch of the selected state at stationarity. We introduce a framework, rooted in a time-scale separation analysis, which is able to capture leading non-equilibrium features using only equilibrium arguments under well-defined conditions. In particular, it is possible to identify fast-dissipation sub-networks of reactions whose Boltzmann equilibrium dominates the steady-state of the entire system as a whole. Finally, we also show that the dissipated heat (and so the entropy production) can be estimated, under some approximations, through the heat capacity of fast-dissipation sub-networks. This work provides a tool to develop an intuitive equilibrium-based grasp on complex non-isothermal reaction networks, which are important paradigms to understand the emergence of complex structures from basic building blocks.

Light-Switchable Buffers.

A visible light-switchable buffer system based on a merocyanine photoacid is presented. Para-substitution of the indolium side with a methoxy group affords a compound suitable for making hydrolytically stable aqueous buffers whose pH can be tuned between 7 and 4 using 500 nm light.

Prenatal genetic diagnosis of cranioectodermal dysplasia in a Polish family with compound heterozygous variants in WDR35.

The ciliary chondrodysplasias represent a group of clinically and genetically heterogeneous disorders that affect skeleton development. Cilia are organelles that project from the surface of many cell types and play an important role during prenatal and postnatal human development. Cranioectodermal dysplasia (Sensenbrenner syndrome, CED) is a ciliopathy primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. To date six genes have been associated with CED: IFT122, WDR35, WDR19, IFT140, IFT43, and IFT52. Prenatal diagnosis of CED is challenging, and genetic testing can facilitate making a correct diagnosis. Here, we report on a family with two male siblings affected by CED: a 3.5 year-old patient and his 2 year-old brother. Molecular analysis of the proband at 1 year of age revealed compound heterozygous variants in WDR35: c.3G>A [p.(Met1-Ala30delinsMetfsTer4)] and c.2522A>T [p.(Asp841Val)]. Ultrasound examination during the second pregnancy revealed an increased nuchal translucency of 4.5 mm and a hypoplastic nasal bone at 12 weeks of gestation. Prenatal diagnostic testing was offered because of an increased risk for chromosomal abnormalities and recurrence risk for CED. Prenatal genetic analysis of a chorionic villus sample detected the WDR35 variants previously identified in the elder brother. This is the first report of a prenatal genetic diagnosis in CED.

Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1 versus placebo as a prophylaxis for recurrence urinary tract infections in children: a study protocol for a randomised controlled trial.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections in children. In children < 7 years of age, the prevalence of one episode of symptomatic UTI has been estimated at 3-7% in girls and 1-2% in boys, whereas 8-30% of them will have one or more episodes of UTI. The use of some probiotics appears to reduce the risk of recurrence of UTIs. Since the effects of probiotics are strain-specific, the efficacy and safety of each strain has to be assessed. The main aim of this study is to determine whether probiotics (containing Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1) therapy are effective in preventing UTI in children compared to placebo. METHOD: A superiority, double-blind, randomised, controlled trial is being conducted. One hundred and six patients aged 3 to 18 years with recurrent UTIs in last year (defined as: ≥ 2 episodes of UTI with acute pyelonephritis/upper UTI; or 1 episode of UTI with acute pyelonephritis and ≥ 1 episodes of UTI with cystitis/lower UTI; or ≥ 3 episodes of UTI with cystitis/lower UTI) or children with ≥ 1 infection in the upper urinary tract and ≥ 1 of recurrent UTIs risk factors (congenital anomalies of the kidney and urinary tract, constipation, bladder dysfunction, myelomeningocele, sexual activity in girls) will be randomly assigned to receive a 90-day prophylaxis arm (probiotic containing L. rhamnosus PL1 and L. plantarum PM1) or a 90-day placebo arm. The primary outcome measure will be the frequency of recurrence of UTI during the intervention and in the period 9 months after the intervention. DISCUSSION: The findings of this randomised controlled trial (RCT), whether positive or negative, will contribute to the formulation of further recommendations on prevention of recurrent UTIs in children. TRIAL REGISTRATION NUMBER: NCT03462160, date of trial registration 12th March 2018.

[The CIMH Track Concept in Psychiatry: Syndrome-specific Treatment across Modalities - Part 2 - Practical implementation]. / Das ZI-Track-Konzept in der modernen Psychiatrie: Eine syndromspezifische sektorenübergreifende Behandlung.

Modern psychiatry needs to implement novel mental health care systems in order to address recent developments in diagnostics and treatment of psychiatric patients. In this context, it is necessary to take into account recent ethical and certain legal aspects which explicitly seek to reduce coercive treatment. The so-called "track-unit" is a promising strategy in order to achieve these goals. The "track-unit" seeks to enhance and improve patients' autonomy, setting-overlapping team continuity, compliance and adherence to treatment as well as to reduce time of patients in hospital as inpatients by more flexible intervention. Although there are many interfaces between normal wards and the "track-unit", implementation into daily routine should be done gradually. The first part of this paper will focus on required changes taking as an example the Department of Psychiatry and Psychotherapy at the Central Institute of Mental Health in Mannheim. In the second part, we will describe corresponding helpful constructional measures. In part three, we will discuss the socio-economic aspects and benefits of "track-units". In conclusion, the implementation of "track-units" in a German psychiatric department is a personnel and economic endeavor to improve the link and coordination between diagnostics and treatment throughout all stages of mental illness.

[The CIMH Track Concept in Psychiatry: Syndrome-specific Treatment across Modalities - Part 1 - Theoretical background]. / Das ZI-Track-Konzept in der modernen Psychiatrie: Eine syndromspezifische sektorenübergreifende Behandlung.

During the past decades, important progress was made in the treatment of patients with mental disorders. Nevertheless, the guideline-based treatment still represents a significant challenge that must take into account novel diagnostic and therapeutic possibilities as well as recent social development and the economic framework. Therefore, there is a need for further improvement of care in inpatient, day-care and outpatient hospital units. An effective and economic over-arching treatment setting may be the so called "Track-unit". This is a symptom- and syndrome-based, decentralised, and modular constructed unit adjusted to the patient's individual stage-specific needs for his / her treatment across in- and outpatient sectors. This concept allows a team of clinicians to accompany a patient from acute (even coercive) admission through to discharge and outpatient department in order to ensure the best-fitted treatment providing a maximum continuity of care without break-points in responsibilities and information flow. The Track-unit may improve the quality of mental health care while at the same time meeting economic and social interests. However, its implementation is challenging for both staff and internal processes. Here, we focus on underlying principles of the Track-concept in a German psychiatric department emphasizing ethical, therapeutic, personnel, and educational benefits of this alternative and promising setting in modern psychiatry.

Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD). METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age- and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses. RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-κ-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls. CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.

Correlation of differential ascites volume with primary cytoreductive surgery outcome, lymph node involvement, and disease recurrence in advanced ovarian cancer.

OBJECTIVE: High-grade serous ovarian cancer accounts for a disproportionate number of deaths from gynecologic malignancies. It typically presents at an advanced stage and with a high volume of ascites a common presenting feature. The aims of this study is to evaluate the association between ascites volume at the time of primary surgery for advanced stage ovarian cancer with surgical outcomes and patterns of recurrence. METHODS: A retrospective review of stage III/IV high-grade serous ovarian cancer patients who underwent primary surgery at two centers between March 2003 to June 2016. Patients were categorized as low-volume ascites (≤ 200 mL) vs high-volume (≥ 1 L). Patients with an unknown volume of ascites or neoadjuvant chemotherapy were excluded. Patients' characteristics were compared for the two groups. Probability of recurrence over time and the HR from a proportional hazards model for sub-distribution were calculated. RESULTS: A total of 210 patients were included, 90 (42.9%) patients in the low-volume and 120 (57.1%) patients in the high-volume group. Patients in the low-volume group were older with a median age of 60.2 years vs 56.8 years in the high-volume group and had lower serum CA-125 levels (mean 223 vs 971.5 U/mL). The low-volume group had better surgical outcome with suboptimal debulking (> 1 cm residual disease) in only 17.8 % vs 39.2 % in the high-volume group and had longer median time to recurrence (2.8 years in low-volume vs 1.6 years high-volume group). At the time of recurrence, the low-volume group had a less disseminated pattern of recurrence, lower rates of ascites (20 % in the low-volume group vs 37.2 % in the high-volume group), and a trend toward lower serum CA125 levels (mean 352.8 vs 596.9 U/mL). CONCLUSIONS: Advanced stage serous ovarian cancer patients who present with low-volume ascites have lower serum CA125 levels, more optimal cytoreduction rates, and longer disease-free interval. The low-volume group had less ascites, less disseminated disease, and a trend toward lower serum CA125 levels at the time of recurrence.

Is copeptin a reliable biomarker of primary monosymptomatic nocturnal enuresis?

INTRODUCTION: The position of copeptin (C-terminal fragment of antidiuretin propeptide) as a marker of primary monosymptomatic nocturnal enuresis (PMNE) is under debate, and there are no data on the relation between copeptin and clinical and biochemical parameters in these patients. Aim of the study was to assess the level of serum copeptin in children with PMNE and to look for a relation between copeptin and selected clinical and biochemical parameters in these children. MATERIAL AND METHODS: Twenty-five children recruited for the trial fulfilled the following criteria: clinical diagnosis of PMNE, age 5-15 years, normal creatinine level, normal ultrasonographic image of kidneys and urinary tract. The following parameters were evaluated: serum copeptin, creatinine, sodium, potassium, hematocrit and urine specific gravity. Twenty healthy children were included in the control group. RESULTS: Children from study and control groups did not differ in serum copeptin, sex, age creatinine, sodium, hematocrit and specific gravity. Serum potassium level remained normal in subjects but was significantly higher in the study group. In children with PMNE we found no relation between serum copeptin level and sex, kidney function, sodium, and urinary specific gravity. We found a negative correlation between copeptin and bladder capacity and trends towards positive relations between copeptin and age, as well as hemoglobin. In the subgroup of children with normal bladder capacity a trend towards a positive correlation between copeptin and potassium was found. CONCLUSIONS: Copeptin may be a marker of hydration status in children with PMNE. The relation between potassium and copeptin levels and the clinical significance of the relation require further studies.

The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women.

PURPOSE: Xenobiotic metabolism is related to the interplay between diet and breast cancer (BC) risk. This involves detoxification enzymes, which are polymorphic and metabolise various dietary metabolites. An important characteristic of this pathway is that chemoprotective micronutrients can act not only as substrates but also as inducers for these enzymes. We investigated whether functional GSTP1 (p.Ile105Val-rs1695), NAT2 (590G>A-rs1799930) SNPs and GSTM1 and GSTT1 deletion polymorphisms could modulate the effect of the Mediterranean diet (MD) on BC risk, in Greek-Cypriot women. METHODS: Genotyping was performed on women from the MASTOS case-control study of BC in Cyprus. A 32-item food-frequency questionnaire was used to obtain dietary intake information. A dietary pattern, which closely resembles the MD (high loadings of vegetables, fruit, legumes and fish), was previously derived with principal component analysis and was used as our dietary variable. RESULTS: GSTT1 null genotype increased BC risk compared with the homozygous non-null GSTT1 genotype (OR 1.21, 95 % CI 1.01-1.45). Increasing adherence to the MD reduced BC risk in women with at least one GSTP1 Ile allele (OR for Ile/Ile = 0.84, 95 % CI 0.74-0.95, for Ile/Val = 0.73, 95 % CI 0.62-0.85) or one NAT2 590G allele (OR for 590 GG = 0.73, 95 % CI 0.63-0.83, for 590 GA = 0.81, 95 % CI 0.70-0.94). p interaction values were not, however, statistically significant. CONCLUSION: The homozygous null GSTT1 genotype could be a risk allele for BC among Greek-Cypriot women. The anticarcinogenic effects of the high adherence to MD against BC risk could also be further enhanced when combined with the wild-type alleles of the detoxification GSTP1 or NAT2 SNPs.

Diagnostic difficulties in a patient with paroxysmal cold haemoglobinuria and acute kidney injury.

Paroxysmal cold haemoglobinuria (PCH) is a form of autoimmune haemolytic anaemia (AIHA) characterised by a sudden onset of haemoglobinuria, either spontaneously or following exposure to cold. In children, it is commonly seen following a viral illness or after immunisation. Diagnosis of PCH is confirmed by a positive Donath Landsteiner (DL) test in which biphasic haemolysins are detected. However, in a real clinical setting, the serological diagnosis of PCH is not always easy. PCH can cause tubular renal injury, which in turn can lead to renal impairment. We describe a case of a two-year-old boy who was admitted to the hospital with pallor, jaundice, dehydration, and dark urine. Two weeks before admission, the child had an upper respiratory tract infection. Laboratory tests showed severe anaemia (haemoglobin 4.5g/dl, haematocrit 11.5%, LDH 8525 U/l), hyperbilirubinaemia (104 µmol/l), haemoglobinuria, and acute kidney injury: GFR 43.9 ml/min/1.73 m2 (grade 2 according to Acute Kidney Injury Network). The direct antiglobulin test was positive for C3c and C3d complement components. The diagnosis of PCH was confirmed by the presence of biphasic antibodies in a DL test on the third day of hospitalisation. The patient received supportive treatment.

Carbamazepine behaviour and effects in an urban wastewater MBR working with high sludge and hydraulic retention time.

The behaviour and fate of carbamazepine (CBZ) in urban wastewater treatment by a membrane bioreactor (MBR) and its possible effects on the system's efficiency, and on mixed microbial communities, has been studied. The experimental microfiltration MBR system, with capacity to treat 10.8 m(3) d(-1) of urban wastewater, operated with a pre-denitrification configuration with high sludge and hydraulic retention time. The CBZ concentration assayed was higher than in the usual urban wastewater, in order to provoke a strong biomass reaction. Influent, effluent, and all bioreactors of the MBR system were analysed in order to calculate a CBZ balance. Bench-scale experiments and respirometric analyses were performed, with and without the presence of CBZ, to evaluate its influence on the bacterial activity. The respirometric assays showed variations in the oxygen uptake rate (OUR) in the presence of CBZ. Negative effects were detected in the MBR bacterial community during the initial period of dosing. However, the effects were not permanent and the biomass spiked with CBZ had behaviour similar to that of the biomass without CBZ after a few hours. Biodegradation was not detected during the MBR treatment. The system showed an inefficient elimination of CBZ (less than 10%) with a high concentration in the effluent. The small percentage of CBZ removal was associated with the sludge retention and eliminated by the purge. All CBZ present in the influent was accounted for, and even an increase in the total amount of CBZ was registered in the permeate. During and after the experimental process, CBZ did not significantly affect the efficiency of the MBR system, and the quality of the effluent was not affected by the dosing of CBZ in terms of COD and nitrogen removal.

Prevalence and effects of caregiving on children.

AIM: This paper reports the prevalence and its related sociodemographic factors of informal caregiving by underage children in Austria. The quantity and intensity of caregiving activities, the motivation for and effects of caregiving and how this differs from non-caregiving children were investigated. BACKGROUND: Young carers are a worldwide phenomenon. Due to methodological and sampling problems, little quantitative data are available. DESIGN: Cross-sectional, descriptive study. METHODS: Based on a random selection of 85 schools and 474 classes, a total of 7403 children aged 10-14 years completed a self-reporting questionnaire that asked for children's help in their families. Descriptive and inferential statistics were used to analyse the data. RESULTS: In the sample, 4·5% caregiving children were identified. The average age of young carers was 12·5 years. Most young carers were female (69·8% vs. 52·7% in the non-young carers group). Young carers assumed more responsibilities (household tasks, general care and sibling care) than their peers. They showed a higher level of physical (e.g. headache 38·2% vs. 24·4%) and mental (e.g. to worry about 68·1% vs. 41·8%) adverse effects than non-young carers. Extrapolation suggests a rate of 3·5% young carers in underage children of 5-18 years in Austria. CONCLUSION: Data on national level are essential preconditions to initiate support for young carers. Nurses can promote children's health and well-being through prevention of an inappropriate caregiving role.

Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1 versus Placebo as Prophylaxis for Recurrence of Urinary Tract Infections in Children.

Urinary tract infections (UTIs) rank among the most prevalent bacterial infections in children. Probiotics appear to reduce the risk of recurrence of UTIs. This study aimed to evaluate whether probiotics containing Lactobacillus rhamnosus PL1 and Lactobacillus plantarum PM1 therapy prevent UTIs in the pediatric population compared to a placebo. A superiority, double-blind, randomized, controlled trial was conducted. In total, 54 children aged 3-18 years with recurrent UTIs or ≥one acute pyelonephritis and ≥one risk factor of recurrence of UTIs were randomly assigned (27 patients in each arm) to a 90-day probiotic or placebo arm. The age, sex, diagnosis, renal function, risk factors, and etiology of UTIs did not vary between the groups. During the intervention, 26% of children taking the probiotic had episodes of UTI, and it was not significantly less than in the placebo group. The number of UTI episodes during the intervention and the follow-up period decreased significantly in both groups, but the difference between them was insignificant. We observed a decrease in UTIs during the study of almost 50% in the probiotic group compared to the placebo group. Probiotics can be used as natural, safe prophylaxis for children with risk factors for UTIs in whom antibiotic prevention is not indicated.

Use of the Gene Expression Test Prosigna® in Premenopausal Patients with HR+, HER2- Early Breast Cancer: Correlation of the Results with the Proliferation Marker Ki-67.

Introduction: In hormone receptor-positive (ER+/PR+) and human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (EBC), gene expression tests such as the Prosigna are increasingly used since classic clinicopathological parameters and the proliferation factor Ki-67 often do not allow a definite therapy decision regarding an adjuvant chemotherapy. While the Prosigna test has been validated for postmenopausal patients, few data are available regarding its use in premenopausal patients. The present study compared the Prosigna test with the Ki-67 index in premenopausal patients. Materials and Methods: Premenopausal patients with HR+ HER2-, pN0-1, G1-2 EBC were retrospectively enrolled (n = 55). The Prosigna assay was performed in formalin-fixed paraffin-embedded tumor samples of surgical resection specimens. Ki-67 was reassessed in original diagnostic core needle biopsy specimens and defined as low, intermediate, or high with the threshold of <10%, 10-24%, ≥25%. Results: According to Ki-67, patients were in the low (LR)-, intermediate (IR)-, and high-risk (HR) groups in 40%, 36%, and 24% of the cases. The Prosigna gene signature assay assessed the risk of recurrence as LR for 45% of the patients, IR for 35%, and HR for 20%. The most frequent intrinsic subtypes were luminal A in 73% and luminal B in 24% of the patients. A moderate correlation was found between Prosigna and Ki-67 scores with a Pearson correlation coefficient of 0.51. In the overall cohort, 47% of the Ki-67-based therapy decision would correspond to those based on the Prosigna score. After exclusion of IR patients, matching of low/low or high/high results was observed in 57% of the cases. Conclusion: According to the present study, there is only limited concordance regarding the risk group stratification between Ki-67 and Prosigna-based risk assessment. The relevance and frequency of premenopausal breast cancer emphasizes the need for further evaluation of gene expression analyses in this setting and the correlation with classic clinicopathological parameters regarding therapy decision-making.

[Hypertensive crisis in children and adolescents]. / Przelom nadcisnieniowy u dzieci i mlodziezy.

Hypertensive crisis is a sudden rise in blood pressure above 99 c. for sex, age and height +5 mm Hg. Depending on patient's symptoms, hypertensive crisis can be divided into hypertensive emergency severe arterial hypertension with target organ insufficiency and/r damage (central nervous system, heart, kidney, eye), and hypertensive urgency - severe arterial hypertension without target organ insufficiency and damage with non-specific symptoms like: headaches, vertigo, nasal bleeding, nausea, and vomiting. The most common causes of hypertensive crisis in neonates and infants are renal artery thrombosis, broncho-pulmonary dysplasia, and coarctation of aorta; in older children - kidney diseases and renal artery stenosis. In neonates and infants symptoms of cardiac failure predominate, whereas in older children symptoms from central nervous system (headaches, nausea, vomiting, changes in level of consciousness, seizures, focal deficits). Hypertensive crisis is treated with fast- and short-acting medications; 25% reduction of blood pressure within first 8 hours is recommended, with complete normalization within 24-48 hours. Hypertensive emergency should be treated with intravenous agents (labetalol, hydralazine, nicardipine, and sodium nitroprusside), hypertensive urgency with intravenous or oral agents like nifedipine, isradipine, clonidine and minoxidil. Nicardipine is a first-choice medication in neonates.