Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

BACKGROUND: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group). OBJECTIVES: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis. MATERIAL AND METHODS: The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis. RESULTS: Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85-89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy. CONCLUSIONS: We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population.

A cross talk between microbial metabolites and host immunity: Its relevance for allergic diseases.

BACKGROUND: Allergic diseases, including respiratory and food allergies, as well as allergic skin conditions have surged in prevalence in recent decades. In allergic diseases, the gut microbiome is dysbiotic, with reduced diversity of beneficial bacteria and increased abundance of potential pathogens. Research findings suggest that the microbiome, which is highly influenced by environmental and dietary factors, plays a central role in the development, progression, and severity of allergic diseases. The microbiome generates metabolites, which can regulate many of the host's cellular metabolic processes and host immune responses. AIMS AND METHODS: Our goal is to provide a narrative and comprehensive literature review of the mechanisms through which microbial metabolites regulate host immune function and immune metabolism both in homeostasis and in the context of allergic diseases. RESULTS AND DISCUSSION: We describe key microbial metabolites such as short-chain fatty acids, amino acids, bile acids and polyamines, elucidating their mechanisms of action, cellular targets and their roles in regulating metabolism within innate and adaptive immune cells. Furthermore, we characterize the role of bacterial metabolites in the pathogenesis of allergic diseases including allergic asthma, atopic dermatitis and food allergy. CONCLUSION: Future research efforts should focus on investigating the physiological functions of microbiota-derived metabolites to help develop new diagnostic and therapeutic interventions for allergic diseases.

Does PM 2.5 and PM 10-associated heavy metals affect short-term and long-term survival after out-of-hospital cardiac arrest? Four-year study based on regional registry.

BACKGROUND: This study aims to investigate the effect of arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb) suspended on particulate matters (PM) 2.5 and PM 10 taking into account clinical factors on 30-day and one-year survival after out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective 4-year study that involved patients hospitalized after OHCA. Patients' data were obtained from Emergency Medical Services dispatch cards and the National Health Fund. The concentration of air pollutants was measured by the Environmental Protection Inspectorate in Poland. RESULTS: Among the 948 patients after OHCA, only 225 (23.7%) survived for 30 days, and 153 (16.1%) survived for 1 year. Survivors were more commonly affected by OHCA in urban areas (85 [55.6%] vs. 355 [44.7%]; P=0.013) and had slightly higher one-year mean concentration of As (0.78 vs. 0.77; P=0.01), Cd (0.34 vs. 0.34; P=0.012), and Pb (11.13 vs. 10.20; P=0.015) with no differences in daily mean concentration. Significant differences in mean concentrations of heavy metals and PM 2.5 and PM 10 were observed among different quarters. However, survival analysis revealed no differences in long-term survival between quarters. Heavy metals, PM 2.5, and PM 10 did not affect short-term and long-term survival in multivariable logistic regression. CONCLUSIONS: The group of survivors showed slightly higher mean one-year concentrations of As, Cd and Pb, but they also experienced a higher incidence of OHCA in urban areas. There were no differences in long-term survival between patients who suffer OHCA in different quarters. Heavy metals did not independently affect survival.

Risk factors for cardiovascular diseases: the focus on primary prevention.

Views on the etiopathogenesis of atherosclerosis are subject to evolution. In addition to the classic well-known risk factors, new ones related to mental state, social life and environment are being discovered. Both acute and chronic stress stimulate inflammatory processes. Due to the change in lifestyle and eating habits, the accumulation of risk factors in childhood is an increasing problem. Knowledge of risk factors allows for effective primary prevention of cardiovascular diseases. The effectiveness of prevention increases when the activities cover the largest possible part of the society, and access to a doctor is easy. Therefore, government programs are being implemented offering patients easier access to diagnostics of cardiovascular diseases at the level of primary health care, which enables faster identification of people at the greatest cardiovascular risk. Easier access to primary care and a good doctor-patient relationship improve patient compliance. In this situation, the importance of the family doctor as a key link in the diagnosis, prevention and treatment of cardiovascular diseases is increasing.

Cytomegalovirus Infection in Pregnancy Prevention and Treatment Options: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options. METHODS: Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review. RESULTS: A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = -0.479, 95% CI = -0.977 to 0.019, p = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV). CONCLUSIONS: The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options.

Role of First Trimester Screening Biochemical Markers to Predict Hypertensive Pregnancy Disorders and SGA Neonates-A Narrative Review.

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as ß-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD.

The Effect of Daylight-Saving Time on Percutaneous Coronary Intervention Outcomes in Acute Coronary Syndrome Patients-Data from the Polish National Registry of Percutaneous Coronary Interventions (ORPKI) in the Years 2014-2022.

INTRODUCTION: Many factors related to the switch to summer/winter time interfere with biological rhythms. OBJECTIVES: This study aimed to analyze the impact of time change on clinical outcomes of patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Electronic data of 874,031 patients with ACS who underwent invasive procedures were collected from the Polish National Register of Interventional Cardiology Procedures (ORPKI) between 2014 and 2021. We determined the number of patients undergoing PCI and periprocedural mortality during the day of spring or autumn time change and within the first 3 and 7 days after the time change. RESULTS: We demonstrated the impact of time changes on the periprocedural mortality of ACS patients within 1 day and the period of 3 and 7 days from the time change. We observed that the occurrence of all ACS and NSTEMI on the first day was lower for both time changes and higher in the case of UA and spring time change. The autumn time change significantly reduced the occurrence of all types of ACS. A significant decrease in the number of invasive procedures was found after autumn transition in the period from the first day to 7 days for ACS, NSTEMI, and UA. CONCLUSIONS: The occurrence of ACS and the number of invasive procedures were lower for both changes over time. Autumn time change is associated with increased periprocedural mortality in ACS and a less frequent occurrence of UA and NSTEMI within 7 days.

Ultrasonographic Signs of Cytomegalovirus Infection in the Fetus-A Systematic Review of the Literature.

BACKGROUND: congenital cytomegalovirus (cCMV) infection during pregnancy is a significant risk factor for fetal and neonatal morbidity and mortality. CMV detection is based on the traditional ultrasound (US) and MRI (magnetic resonance) approach. METHODS: the present review used the PRISMA protocol for identification of studies associated with CMV infection and sonographic analysis. Various search terms were created using keywords which were used to identify references from Medline, Pubmed, PsycInfo, Scopus and Web of Science. RESULTS: sonographic analysis of the cCMV infection identified several of the key features associated with fetuses. The presence of abnormal patterns of periventricular echogenicity, ventriculomegaly and intraparenchymal calcifications is indicative of CMV infection in the fetus. Hyperechogenic bowels were seen frequently. These results correlate well with MRI data, especially when targeted transvaginal fetal neurosonography was carried out. CONCLUSIONS: ultrasonography is a reliable indicator of fetal anomalies, due to cCMV. Fetal brain and organ changes are conclusive indications of infection, but many of the ultrasonographic signs of fetal abnormality could be due to any viral infections; thus, further research is needed to demarcate CMV infection from others, based on the ultrasonographic approach. CMV infection should always be an indication for targeted fetal neurosonography, optimally by the transvaginal approach.

COVID-19 as an independent predictor of aspiration thrombectomy in STEMI. National data from the ORPKI register in the years 2020-2022.

Introduction: Coronavirus disease 2019 (COVID-19) exacerbates intravascular thrombosis that occurs in the coronary artery in ST-elevation myocardial infarction (STEMI). Aim: To analyze the impact of COVID-19 on the application and effect of thrombectomy in STEMI patients. Material and methods: 29915 STEMI patients were analyzed, of whom 3139 (10.5%) underwent thrombectomy. COVID-19 (+) was reported in 311 (10.8%). The clinical characteristics and management of STEMI in COVID-19 (+) and COVID-19 (-) patients were compared. A multivariable logistic regression analysis was performed in search of factors influencing thrombectomy. Results: COVID-19 (+) patients had higher Killip class (IV class; n = 33 (12.31%) vs. n = 138 (5.84%); p < 0.0001) and cardiac arrest at baseline was more frequent in this group (n = 25 (8.04%) vs. n = 137 (4.84%); p = 0.016). Thrombolysis in myocardial infarction (TIMI) 3 after percutaneous coronary intervention was less frequent (n = 248 (80.52%) vs. n = 2388 (87.19%); p = 0.001) in the COVID-19 (-) group. Periprocedural mortality was similar in both groups (n = 28 (0.99%) vs. n = 4 (1.29%); p = 0.622). In multivariable regression analysis COVID-19 increased the risk of thrombectomy (OR = 1.23; 97.5% CI: 1.05-1.43; p = 0.001). Conclusions: STEMI patients undergoing aspiration thrombectomy who were COVID-19 (+) were more likely to be in a severe clinical condition (higher Killip class, more frequent cardiac arrest before the procedure) than COVID-19 (-) patients. Despite more intensive antiplatelet and anticoagulant treatment, PCI procedures were less likely to result in an optimal TIMI 3 effect. COVID-19 is an independent strong predictor of patient qualification for aspiration thrombectomy in STEMI.

Glomus sp. and Bacillus sp. strains mitigate the adverse effects of drought on maize (Zea mays L.).

Maize (Zea mays L.) is an economically important source of food and feed. This species is highly sensitive to drought, which is the most limiting factor for the biomass yield of a crop. Thus, maize cultivation methods should be improved, especially by environment-friendly agricultural practices, such as microorganisms. Here, we provide evidence that Glomus sp. and Bacillus sp. modulate maize response to drought. Inoculation of maize seeds by these microorganisms restored the proper photosynthetic activity of the plant under drought and stabilized the osmoprotectant content of the leaf. The beneficial effect of Glomus sp. and Bacillus sp. was also related to the stabilization of cell redox status reflected by hydrogen peroxide content, antioxidant enzymes, and malondialdehyde level in leaves. As we revealed by several methods, shaping maize response to drought is mediated by both microorganism-mediated modifications of cell wall composition and structure of leaves, such as downregulating pectin, affecting their methylation degree, and increasing hemicellulose content. Overall, we provide new information about the mechanisms by which Glomus sp. and Bacillus sp. induce drought tolerance in maize, which is a promising approach for mitigating abiotic stresses.

Jasmonate-Dependent Response of the Flower Abscission Zone Cells to Drought in Yellow Lupine.

Lipid membranes, as primary places of the perception of environmental stimuli, are a source of various oxygenated polyunsaturated fatty acids-oxylipins-functioning as modulators of many signal transduction pathways, e.g., phytohormonal. Among exogenous factors acting on plant cells, special attention is given to drought, especially in highly sensitive crop species, such as yellow lupine. Here, we used this species to analyze the contribution of lipid-related enzymes and lipid-derived plant hormones in drought-evoked events taking place in a specialized group of cells-the flower abscission zone (AZ)-which is responsible for organ detachment from the plant body. We revealed that water deficits in the soil causes lipid peroxidation in these cells and the upregulation of phospholipase D, lipoxygenase, and, concomitantly, jasmonic acid (JA) strongly accumulates in AZ tissue. Furthermore, we followed key steps in JA conjugation and signaling under stressful conditions by monitoring the level and tissue localization of enzyme providing JA derivatives (JASMONATE RESISTANT1) and the JA receptor (CORONATINE INSENSITIVE1). Collectively, drought-triggered AZ activation during the process of flower abscission is closely associated with the lipid modifications, leading to the formation of JA, its conjugation, and induction of signaling pathways.

Anti-tumor effects of rigosertib in high-risk neuroblastoma.

High-risk neuroblastoma has a poor prognosis despite intense treatment, demonstrating the need for new therapeutic strategies. Here we evaluated the effects of rigosertib (ON-01910.Na) in preclinical models of high-risk neuroblastoma. Among several hundred cancer cell lines representing 24 tumor types, neuroblastoma was the most sensitive to rigosertib. Treatment of MYCN-amplified neuroblastoma organoids resulted in organoid disintegration, decreased cell viability, and increased apoptotic cell death. Neuroblastoma response to rigosertib involved G2M cell cycle arrest and decreased phosphorylation of AKT (Ser473) and ERK1/2 (Thr202/Tyr204). Rigosertib delayed tumor growth and prolonged survival of mice carrying neuroblastoma MYCN-amplified PDX tumors (median survival: 31 days, treated; 22 days, vehicle) accompanied with increased apoptosis in treated tumors. We further identified vincristine and rigosertib as a potential promising drug combination treatment. Our results show that rigosertib might be a useful therapeutic agent for MYCN-amplified neuroblastomas, especially in combination with existing agents.

EPIP-Evoked Modifications of Redox, Lipid, and Pectin Homeostasis in the Abscission Zone of Lupine Flowers.

Yellow lupine is a great model for abscission-related research given that excessive flower abortion reduces its yield. It has been previously shown that the EPIP peptide, a fragment of LlIDL (INFLORESCENCE DEFICIENT IN ABSCISSION) amino-acid sequence, is a sufficient molecule to induce flower abortion, however, the question remains: What are the exact changes evoked by this peptide locally in abscission zone (AZ) cells? Therefore, we used EPIP peptide to monitor specific modifications accompanied by early steps of flower abscission directly in the AZ. EPIP stimulates the downstream elements of the pathway-HAESA and MITOGEN-ACTIVATED PROTEIN KINASE6 and induces cellular symptoms indicating AZ activation. The EPIP treatment disrupts redox homeostasis, involving the accumulation of H2O2 and upregulation of the enzymatic antioxidant system including superoxide dismutase, catalase, and ascorbate peroxidase. A weakening of the cell wall structure in response to EPIP is reflected by pectin demethylation, while a changing pattern of fatty acids and acyl lipids composition suggests a modification of lipid metabolism. Notably, the formation of a signaling molecule-phosphatidic acid is induced locally in EPIP-treated AZ. Collectively, all these changes indicate the switching of several metabolic and signaling pathways directly in the AZ in response to EPIP, which inevitably leads to flower abscission.

The interaction of linguistic and arithmetic factors affects adult performance on arithmetic word problems.

Performance on word problems is influenced by linguistic and arithmetic factors, and by their interaction. To study these factors and interactions, we manipulated linguistic and arithmetic factors independently in a within-participant design that included complexity parameters (a) in the domain of arithmetic: carry/borrow (no-carry/borrow vs. carry/borrow), operation (addition vs. subtraction), (b) in the domain of linguistics: nominalization (nominalized vs. verbalized form), and (c) linking the two domains: lexical consistency (linguistic predicate locally consistent vs. inconsistent with mathematical operation). Response times of 25 students solving 320 one-step word problems were measured. All four factors showed a main effect on response times, and interactions between linguistic and arithmetic factors affected response times. These interactions were observed when the linguistic and arithmetic factors were conceptually linked. Our results highlight that not only the linguistic and arithmetic complexities of an item contribute to the difficulty of a word problem, but linguistic and arithmetic factors interact. We discuss the theoretical implications for the numerical and the linguistic domain as well as the possible impact of domain-general characteristics, such as working memory limitations as a potential reason for the observed interactions between numerical and linguistic attributes.

Word problems: a review of linguistic and numerical factors contributing to their difficulty.

Word problems (WPs) belong to the most difficult and complex problem types that pupils encounter during their elementary-level mathematical development. In the classroom setting, they are often viewed as merely arithmetic tasks; however, recent research shows that a number of linguistic verbal components not directly related to arithmetic contribute greatly to their difficulty. In this review, we will distinguish three components of WP difficulty: (i) the linguistic complexity of the problem text itself, (ii) the numerical complexity of the arithmetic problem, and (iii) the relation between the linguistic and numerical complexity of a problem. We will discuss the impact of each of these factors on WP difficulty and motivate the need for a high degree of control in stimuli design for experiments that manipulate WP difficulty for a given age group.

[Enterobacter cloacae--antimicrobial susceptibility of strains isolated from hospitalized patients in 2004-2005]. / Enterobacter cloacae--wrazliwosc na antybiotyki szczepów izolowanych od chorych hospitalizowanych w latach 2004-2005.

The profiles of resistance of ESBL(-) and ESBL(+) strains of Enterobacter cloacae were analysed and compared. 466 Enterobacter cloacae strains isolated from different specimens obtained from patients of big Warsaw hospital in 2004-2005 were investigated. By using the several phenotypic methods 33.5% of strains was identified as ESBL(+). ESBL(+) strains were significantly less susceptible then ESBL(-). These two groups differed mostly in susceptibility to aminoglycosides and fluoroquinolones, e.g. 65.5% of ESBL(-) strains were susceptible to gentamicin, compared to only 25.0% ESBL(+), in case of ciprofloxacin 59.0% of ESBL(-) were susceptible whereas only 25.0% of ESBL(+) strains. The percentage of ESBL(+) grew from 26.4% in 2004 to 40.4% in 2005, whereas a tendency of growing susceptibility to aminoglycosides and fluoroquinolones was noted among all E.cloacae strains. Susceptibility to combinations of piperacillin or ticarcillin with beta-lactamase inhibitor was rather low among ESBL(+) strains.

[Assessment of the susceptibility of the gram-negative rods isolated from hospitalized patients to cefoperazone/sulbactam]. / Ocena wrazliwosci na cefoperazon/sulbaktam szczepów paleczek gram-ujemnych izolowanych od chorych hospitalizowanych.

The susceptibility to cefoperazone/sulbactam of 197 strains of Gram-negative rods demonstrating an ESBL-positive phenotype was determined. The assortment of the investigated strains was as follows (numbers of strains are given in the brackets): E. cloacae (63), S. marcescens (46), K. pneumoniae (21), P. mirabilis (17), E. coli (9), P. vulgaris (8), P. aeruginosa (20) and A. baumanni (13). 83 strains from 197 were susceptible (42.1%). The MIC values were determined and the disc-diffusion method was performed. The susceptibilities among particular species were as follows (the order of data in the brackets is: % of the susceptible strains/MIC50/MIC90): E. cloacae (54.0/16/64), S. marcescens (23.9/64/> or = 128), K. pneumoniae (38.1/32/64), P. mirabilis (41.2/32/64), E. coli (44.4/32/32), P. vulgaris (75.0/8/32), P. aeruginosa (35.0/32/64), A. baumannii (46.2/32/64). Using disc-diffusion method, for 184 strains the difference between diameter of the inhibition zone around the disc with cefoperazone and the disc with cefoperazone/sulbactam was calculated. This difference amounted 5 mm or more in the case of 76.6% of the investigated strains. The results indicate that the comparison of the inhibition zones around cefoperazone and cefoperazone/sulbactam discs may be an additional method useful for phenotypic detection of ESBL producing organisms. These results highly correlated with results obtained by using analogous test with cefpirome and cefpirome/clavulanic acid (85.6% of concordance).