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In both the global and the domestic approach, the real estate market is a multifaceted domain of study, constituting a specific and imperfect system. Researchers have to rely on increasingly advanced analytical tools to capture the structural complexity of real estate markets. Real estate prices are influenced by contradictory behaviors of market participants. This observation prompted the authors to analyze the income and price elasticity of demand for housing by calculating elasticity coefficients in view of changes in housing prices and the Veblen effect. This problem was analyzed based on a review of the literature and the results of an experiment. The results of the current study can be used to confirm the presence of the Veblen effect on the housing market based on the adopted criteria. The coefficients of price and income elasticity of demand for housing were calculated in view of the price dynamics on the real estate market to paint a more complete picture of reality and explain market processes.

The spatial distribution of real estate in specific geographic locations, real estate transactions, and the prices and values of properties are a highly complex spatial phenomena that should be analyzed with the use of multidimensional methods. Spatial factors are taken into account in the modeling process to increase the reliability of real estate market analyses, and spatial autoregressive models are applied to determine the effect of spatial factors on real estate prices and values.

The patterns and relations between real estate prices and the factors which shape them can be presented, among others, in the form of traditional statistical models, as well as by means of geostatistical methods. In the case of research involving the diagnosis and prediction of transaction prices, the key role is played by the spatial aspect, hence the particular significance of geostatistical methods using spatial information.

Introduction: Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN., Methods: Patients with acute leukemia treated with AZA-VEN at a single institution were included in this prospective observational study., Results: Thirteen patients were enrolled, 46% with treatment-naïve, and 56% with relapsed/refractory disease. Fifty-four percent of patients were males; the median age was 69 years. Six patients (46%) developed COVID-19 during the observation time. The median time to COVID-19 was 24 days from the initiation of AZA-VEN. The 2-month cumulative incidence of COVID-19 was 46.2%. Two patients (33%) succumbed to COVID-19. The 100-day COVID-19-free survival from AZA-VEN initiation was 61%. The median follow-up time was 4.3 months., Discussion/conclusion: COVID-19 constitutes a frequent complication of AZA-VEN treatment in the era of the COVID-19 pandemic, leading to death in a significant proportion of patients., (© 2022 S. Karger AG, Basel.)

Gastrointestinal symptoms are common in critically ill COVID-19 patients. There is currently no generally recognized method of assessing gastrointestinal injury in unconscious or sedated intensive care unit (ICU) patients. I-FABP (intestinal fatty acid binding protein) and citrulline have previously been studied as potential biomarkers of enterocyte damage in various gastrointestinal tract diseases, and changes in the levels of these markers may reflect intestinal wall damage in COVID-19. Patients with critical COVID-19, with diagnosed sepsis, or septic shock requiring ICU treatment were included in the study. Blood samples for citrulline and I-FABP were taken daily from day 1 to 5. I-FABP levels were significantly higher in patients who eventually died from COVID-19 than in survivors, and the optimal I-FABP cut-off point for predicting 28-day mortality was 668.57 pg/mL (sensitivity 0.739, specificity 0.765). Plasma levels of I-FABP, but not citrulline, were associated with significantly higher mortality and appeared to be a predictor of poor outcome in multivariate logistic regression analysis. In conclusion, I-FABP seems to be an effective prognostic marker in critically ill COVID-19 patients. Assessing mortality risk based on intestinal markers may be helpful in making clinical decisions regarding the management of intestinal injury, imaging diagnostics, and potential surgical interventions.

Fibronectin (FN) plays an essential role in the host's response to infection. In previous studies, a significant decrease in the FN level was observed in sepsis; however, it has not been clearly elucidated how this parameter affects the patient's survival. To better understand the relationship between FN and survival, we utilized innovative approaches from the field of explainable machine learning, including local explanations (Break Down, Shapley Additive Values, Ceteris Paribus), to understand the contribution of FN to predicting individual patient survival. The methodology provides new opportunities to personalize informative predictions for patients. The results showed that the most important indicators for predicting survival in sepsis were INR, FN, age, and the APACHE II score. ROC curve analysis showed that the model's successful classification rate was 0.92, its sensitivity was 0.92, its positive predictive value was 0.76, and its accuracy was 0.79. To illustrate these possibilities, we have developed and shared a web-based risk calculator for exploring individual patient risk. The web application can be continuously updated with new data in order to further improve the model.

Salvage autologous hematopoietic stem cell transplantation (auto-HSCT) constitutes a therapeutic option for a group of well-selected patients with relapsed multiple myeloma (MM). However, if an insufficient number of stem cells were harvested and stored before the first auto-HSCT, stem cells need to be remobilized. Patients diagnosed with MM who following relapse after auto-HSCT, had remobilization and afterward, auto-HSCT with remobilized cells were included in this retrospective analysis. Thirty-three patients, 61% males, the median age 61 years, were included. With a median follow-up of 1.8 years, 2-year progression-free survival was 56.2%, non-relapse mortality 4.8%. The 2-year cumulative incidence of t -MDS was 4.9%. Factors important for the outcome were: the quality of response, previous radiotherapy, the time between the first and salvage auto-HSCT. To conclude, salvage auto-HSCT performed with cells procured after the previous auto-HSCT can be efficacious in relapsed MM, especially if a sufficiently long response had been obtained to the first auto-HSCT(s).

Objectives: Relapse of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) belongs to the major causes of treatment failure., Methods: Retrospective multicenter analysis of patients diagnosed with AML or MDS who had hematological relapse after allo-HSCT and were treated with azacitidine for this indication., Results: Twenty-three patients receiving azacitidine as the first treatment of relapse (Group_1) and 8 patients receiving azacitidine after other treatment of relapse (Group_2) were included. There were 68% males, median age at initiation of azacitidine was 53 years (15-66). Median time to relapse was 3.5 months and 6.3 months in Group_1 and Group_2, respectively; median time from relapse to azacitidine 0.2 and 2.3 months. Azacitidine 75 mg/m 2 , days 1-7, was administered in 78% and 75% of patients in Group_1 and Group_2, concomitant DLI in 48% and 50%. With median follow-up of 4.7 and 13.6 months, the median overall survival was 5.9 and 9.5 months. 17% and 37.5% patients proceeded to salvage allo-HSCT, with median OS of 11.6 months and not reached respectively., Conclusions: Azacitidine treatment for hematological relapse is associated with poor outcome; nevertheless, a proportion of patients may benefit from it, including patients receiving subsequent salvage allo-HSCT., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Screening sinonasal evaluation is routinely performed before allogeneic hematopoietic cell transplantation (allo-HCT), however, data supporting such evaluation is inconsistent. O b j e c t i v e s: Assessment of the utility of screening sinonasal evaluation with computed tomography (CT)., Methods: A retrospective analysis of acute leukemia patients who underwent allo-HCT, for whom screening sinonasal CT scans were reevaluated, and for whom Lund-Mackay score (LMS) was calculated. R e s u l t s: Forty-eight patients, the median age at allo-HCT 38 years (18-58), 52% males, were included. 79% had acute myeloid leukemia (AML), 21% acute lymphoblastic leukemia (ALL). Conditioning intensity was myeloablative in 96% of patients, 21% of patients received total body irradiation. 19% of patients had a history of sinusitis before allo-HCT. Screening sinus CT was performed a median of 22 days before allo-HCT. The median LMS was 1 point (0- 10). The severity of sinus abnormalities was: no abnormalities (31%), mild (67%), moderate (2%), severe (0%). Mucosal thickening was the most frequent abnormality (69%). Eleven patients experienced sinusitis after a median of 93 days (11-607) after allo-HCT. 1-year cumulative incidence of sinusitis was 22%. No threshold of LMS and no type of sinus abnormalities were correlated with sinusitis development after allo-HCT. Mild sinus disease at screening did not negatively impact survival in comparison to no sinus disease. C o n c l u s i o n s: Despite the fact, that majority of analyzed patients had either no or mild sinus disease at screening a significant proportion of patients developed sinusitis after allo-HCT. Evaluation of LMS before allo-HCT did not help predict the development of sinusitis after the procedure.

Background: Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC) > 2 mg/dL or estimated glomerular filtration rate (eGFR) < 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria., Patients and Methods: We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR < 60 mL/min, treated with ASCT from 1998 to 2004., Results: The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P < .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC > 1.4 mg/dL and eGFR < 55mL/min., Conclusions: We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Gas and liquid chromatography-mass spectrometry (GC-MS, LC-MS) methods for the determination of angiotensin-converting enzyme inhibitors (ACEIs) and their metabolites in biological material have been reviewed. Since 1980s those hyphenated techniques have been applied to quantitate ACE inhibitors and the dynamic increase in the number of relevant publications can be observed in recent years. Although most of the methods available in the literature were analyses of plasma or serum, assays of blood and urine were also included. Additionally, sample pretreatment methods, separation conditions and ionization modes were overviewed. Some information on chemical structures, cis-trans izomerization and stability of compounds in question was also included. Most of the reported methods were successfully applied to the pharmacokinetic studies in humans.

A simple and sensitive high performance liquid chromatography method for the determination of nabumetone in human plasma is described. The procedure involves liquid-liquid extraction with ethyl acetate and reversed-phase chromatography with fluorimetric detection (excitation 230 nm, emission 356 nm). The chromatographic conditions and the extraction procedure gave a clean chromatogram for the compound. The limit of quantitation was established as 0.313 ng/ml and the calibration curve was linear up to 20 ng/ml. The within-day and between-day relative standard deviations were less than 10% and the accuracy of the assay was in the range of 99-104%. The suitability of the method is shown for pharmacokinetic studies.

The pharmacokinetics and toxicity of (-)-(S)-bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinae 2-oxide, CAS 146452-37-1, CBM-11) were determined in ten patients with non-small cell lung cancer following an oral dose of 1.38 g/m2 B.S.A. (Body Surface Area). The drug was given as a powder in gelatine capsules to fasting patients. Plasma samples were collected during the first 24 h after administration. All samples, after extraction with chloroform, were assayed by a reverse phase HPLC method using UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide showed relatively fast absorption kinetics. Peak concentration of 47 micrograms/ml was observed after 1 h. The average half-life was about 5 h. Toxicities associated with oral (-)-(S)-bromofosfamide therapy consisted of symptoms regarding the central nervous system, gastrointestinal tract and urinary tract. Neurotoxic symptoms were the most common clinically significant side effects and probably dose limiting.

(-)-(S)-Bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinane 2-oxide, CAS 146452-37-1, CBM-11) is a new potential anti-cancer drug, currently under investigation. Its pharmacokinetics and bioavailability were studied in female mice following intravenous and oral administration of the dose of 50 mg/kg. The compound was extracted from plasma samples using chloroform and analyzed by high-performance liquid chromatography with UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide was absorbed quickly, attaining a maximum level of 33.9 micrograms/ml at 5 min, and was eliminated with a half-life (t1/2) of about 0.9 h. The average half-life of intravenously administered (-)-(S)-bromofosfamide was about 0.7 h. The total plasma clearance (CL) and volume of distribution (Vd) were found to be 0.14 l/h and 4.92 l/kg, respectively. The absolute bioavailability of (-)-(S)-bromofosfamide after oral administration was 105%.

A simple and selective analytical method for the determination of buspirone analogue--mesmar in rat plasma is described. The procedure involves liquid-liquid extraction followed by reversed-phase high-performance chromatographic analysis with UV detection at 245 nm. No endogenous compounds were found to interfere. The absolute extraction recovery from plasma samples was 76%. The linearity was assessed in the range 0.12-2.44 nmol/ml. Stability of mesmar during processing (autosampler) and in plasma was checked. This method proved suitable for pharmacokinetic studies following single oral dose in rats.

A specific and sensitive high-performance liquid chromatographic method for the determination of domperidone in human plasma is described. Domperidone was isolated by solid-phase extraction using nitrile SPE cartridges. The drug was eluted with a mixture consisting of methanol-triethylamine-acetic acid, separated on a reversed-phase column, and measured by fluorimetric detection after post-column photoderivatization. The absolute extraction recovery from plasma samples was 83%. The limit of quantitation was established as 1 ng/ml. The relative standard deviation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%, expect with the concentration of 1 ng/ml. The suitability of the method is shown for pharmacokinetic studies.

In this open, randomized, two way crossover, bioequivalence study, two 5 mg tablet preparations of glipizide (Glipizyd tabl. 5 mg, Tarchomińskie Zakłady Farmaceutyczne POLFA S.A., and Glibenese tabl. 5 mg, Pfizer), were compared in 24 healthy male volunteers. Pharmacokinetic variables (mean maximum plasma concentration, mean time to reach maximum plasma concentration, and the mean area under the plasma concentration-time curve) were not statistically significantly different for the two formulations. It can be concluded that the two tablet preparations of glipizide are likely to be bioequivalent.

The effects of phenobarbital (PB), carbamazepine (CBZ) and diazepam (DZ) on total hepatic cytochrome P450, cytochromes P4502B1/2B2 contents and aminopyrine N-demethylase activity was investigated. Adult male rats were treated per os with PB (80 mg/kg/day), CBZ (75 mg/kg/day) or DZ (90 mg/kg/day) for 3 consecutives days. Carbamazepine and phenobarbital produced significant increase of the contents of total cytochrome P450 and cytochromes P4502B1/2B2 as well as aminopyrine N-demethylase activity. In contrast, diazepam decreased the total hepatic cytochrome P450 content. This drug did not affect the level of cytochromes P4502B1/2B2 but increased aminopyrine N-demethylase activity comparing to the control animals.

The combined effect of carbamazepine (CBZ) and raised environmental temperature on total hepatic cytochrome P450 and on cytochromes P4502B1/2B2 contents was investigated. Carbamazepine produced significant increase of the contents of total cytochrome P450 and cytochromes P4502B1/2B2 in rats exposed to 21 degrees C and 28 degrees C. In contrast exposure of rats of 35 degrees C decreased induction capacity of carbamazepine.

A high-performance liquid chromatographic method for the determination of miconazole in human plasma is described. A solid-phase extraction was performed on an octadecyl (C18) cartridge. Miconazole was eluted with methanol, separated on a reversed-phase column and was measured by ultraviolet detection at 230 nm. The absolute extraction recovery from plasma samples was 85%. The limit of detection was established as 5 ng/ml. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%, except with the concentration of 10 ng/ml. The plasma levels of miconazole in twelve healthy volunteers given a 250-mg oral dose of two tablet forms were determined by this method.

Cytosolic liver glutathione S-transferase (GST) activity was decreased for CDNB and DCNB as substrates in long term alloxan induced diabetes. Similar to cytosolic, microsomal glutathione S-transferase activity was also decreased for CDNB. In contrast, both microsomal and cytosolic GST activities for ETA as well as cytosolic and microsomal glutathione (GSH) contents were unaffected. The activity of Se-dependent glutathione peroxidase activity, but not nonSe-dependent peroxidase activity was increased in diabetic rats. The results suggest that diabetic state has a different effect on each isoenzyme of hepatic glutathione S-transferase activity. After insulin treatment of diabetic animals the activities of both cytosolic and microsomal GST was not restored and the activity of non Se-GSHPx was significantly lower than the control value.

In the kidney of diabetic rats the elevated GSH concentration was accompanied with the 25% increase of cytosolic Se-dependent glutathione peroxidase (Se-GSHPx) activity. The activity of cytosol glutathione S-transferase (GST) was decreased to 55% of the control with p-nitrobenzyl chloride, and was unchanged with 1-chloro-2,4-dinitrobenzene, and ethacrynic acid. The activity of GST with cumene hydroperoxide (a good substrate for determination the activity of non Se-GSHPx) in diabetic animals stay unchanged too. Insulin treatment of diabetic rats restores the normal glycemia and the body weight, strongly reduces glucosuria and reverses the morphological changes observed in the kidney. The activity of GST and cytosol Se-GSHPx, as well as GSH content, returned to a normal values after insulin treatment, while the activity of non Se-GSHPx was reduced of about 50% in relation to the control values.

Chemical diabetes produced in male rats by treatment with alloxan (45 mg/kg) decreased aminopyrine N-demethylase activity but not hepatic microsomal protein, cytochrome P-450 and cytochrome b5 contents. In contrast, diabetes increased aniline hydroxylase activity. Glutathione S-transferase activity and the most of the forms of UDP-glucuronyltransferase were decreased but phenolsulphotransferase activity was not affected in alloxan-induced rats. These results suggest that observed changes may led to alteration of drug metabolism and toxicity in diabetes.

Exposure of rats for 3 consecutive days (6 h a day) to 28 degrees C or 35 degrees C does not lead to changes in the induction of hepatic microsomal cytochrome P-450 associated monooxygenases by phenobarbitone as compared with control animals exposed to 21 degrees C. These results suggest that environmental temperature does not change the capacity of phenobarbitone to induce drug metabolizing enzymes in rat liver.

Among the benzodiazepines tested (diazepam, oxazepam, clonazepam, nitrazepam and chlordiazepoxide ) chlordiazepoxide is the most potent inducer of cytochrome P-450, diazepam is a poor inducer, whereas clonazepam and nitrazepam do not possess a capacity to induce of cytochrome P-450. On the other hand, microsomal cytochrome b5 is induced by diazepam only. The extent of induction of cytochrome P-450 and cytochrome b5 depends on the environmental temperature. Chlordiazepoxide is the most potent inducer of cytochrome P-450 in rats exposed to an ambient temperature of 28 degrees C, whereas diazepam have the highest induction ability in rats exposed to 35 degrees C. On the other hand, nitrazepam increased the content of cytochrome b5 in rats exposed to temperature of 35 degrees C only; diazepam was the most potent inducer of cytochrome b5 in rats exposed to temperature of 21 degrees C. These results indicate that high ambient temperature is a factor modifying the ability of benzodiazepines to induce of microsomal cytochrome P-450 and cytochrome b5.

Five benzodiazepines (diazepam, oxazepam, clonazepam, nitrazepam and chlordiazepoxide) were compared with respect to their capacity to affect microsomal aniline hydroxylase, aminopyrine N-demethylase and 4-nitroanisole O-demethylase of rats exposed to the high ambient temperature of 28 degrees C or 35 degrees C. We have stated that the highest effect on the microsomal enzyme activities was observed after chlordiazepoxide, clonazepam or nitrazepam treatments. These results indicate that the presence of nitro group at position 7 or N-oxide at position 4 of benzodiazepine is important for the ability of benzodiazepines to affect the hepatic microsomal enzymes. High environmental temperature modifies the effect of benzodiazepines on tested microsomal enzymes.

Administration of diazepam or oxazepam caused a different response of the rat hepatic microsomal cytochrome P-450 dependent monooxygenase system. Both drugs produced significant decrease in the activity of NADH: cytochrome c oxidoreductase in rats exposed to 21 degrees C, but not to 28 degrees C and 35 degrees C, and did not change the activity of aniline hydroxylase, aminopyrine N-demethylase and 4-nitroanisole O-demethylase and cytochrome b5 level at any tested temperatures. Oxazepam, but not diazepam, caused a decrease in cytochrome P-450 content in rats exposed to 21 degrees C only. The results indicate that the high ambient temperature modifies the effect of tested benzodiazepines on the activity of some microsomal enzymes.

Exposure of rats for 3 h or 6h to 28 degrees C or 37 degrees C led to changes in mixed-function oxidases in liver microsomes as compared with 21 degrees C. The complex pattern of the behaviour of the activities of aniline hydroxylase, 4-nitroanisole-O-demethylase, aminopyrine N-demethylase and NADH: cytochrome c oxidoreductase was not related to the observed decrease of cytochrome P-450 and cytochrome b5 contents.

Short-term exposure of the control and phenobarbitone-treated rats to high ambient temperature caused a different response of the hepatic microsomal cytochrome P-450-dependent monooxygenase system participating in the oxidation of aniline, aminopyrine and p-nitroanisole. The highest differences of the enzyme activities were observed in rats exposed to 28 degrees C, as compared with animals exposed to 21 degrees C or 37 degrees C.

It has been stated that elevation of environment temperature to 28 degrees C or 35 degrees C modifies effects of chlordiazepoxide on activities of rat liver microsomal enzymic systems involved in metabolism of xenobiotics: amidopyrine, aniline and 4-nitroanisole++.