Radon Exposure in the Underground Tourist Route-Historic Silver Mine in Tarnowskie Góry, Poland.

An assessment of the exposure of workers and tourists to radon in the underground tourist route of the Historic Silver Mine in Tarnowskie Góry was carried out. The study was conducted over a one-year period to capture seasonal variations in radon concentrations. CR-39 track detectors were used to measure radon concentrations, which were exposed in the mine during the following periods: 9 February 2021-19 May 2021, 19 May 2021-26 August 2021, 26 August 2021-25 November 2021 and 25 November 2021-3 March 2022. The annual average radon concentration along the tourist route was 1021 Bq m-3. The highest measured concentration was 2280 Bq m-3 and the lowest concentration was 80 Bq m-3. Based on the measured concentrations, effective doses were calculated, assuming that employees spend 1350 h a year in underground areas and that the time of visiting the mine by tourists is ca. 1 h. The average annual effective dose a worker would receive is approximately 2.5 mSv, and a tourist below 2 µSv. The dose limit expressed as the annual effective dose is 1 mSv for members of the general public and 20 mSv for occupational exposure.

Metronomic Chemotherapy in Prostate Cancer.

Despite the significant expansion of the therapeutic armamentarium associated with the introduction of novel endocrine therapies, cytotoxic agents, radiopharmaceuticals, and PARP inhibitors, progression of metastatic castration-resistant prostate cancer (mCRPC) beyond treatment options remains the leading cause of death in advanced prostate cancer patients. Metronomic chemotherapy (MC) is an old concept of wise utilization of cytotoxic agents administered continuously and at low doses. The metronomic is unique due to its multidimensional mechanisms of action involving: (i) inhibition of cancer cell proliferation, (ii) inhibition of angiogenesis, (iii) mitigation of tumor-related immunosuppression, (iv) impairment of cancer stem cell functions, and (v) modulation of tumor and host microbiome. MC has been extensively studied in advanced prostate cancer before the advent of novel therapies, and its actual activity in contemporary, heavily pretreated mCRPC patients is unknown. We have conducted a prospective analysis of consecutive cases of mCRPC patients who failed all available standard therapies to find the optimal MC regimen for phase II studies. The metronomic combination of weekly paclitaxel 60 mg/m2 i.v. with capecitabine 1500 mg/d p.o. and cyclophosphamide 50 mg/d p.o. was selected as the preferred regimen for a planned phase II study in heavily pretreated mCRPC patients.

The Determination of Radon/Thoron Exhalation Rate in an Underground Coal Mine-Preliminary Results.

The objective of this work was to perform a series of measurements of radon and thoron exhalation in the underground workings of an experimental coal mine. In the years 2012-2015, experiments on underground coal gasification were carried out in a coal mine, which caused, among other effects, damage to rock mass. Afterward, periodic increases in the concentration of potential alpha energy (PAEC) of radon decay products in the air were found, which could pose a hazard to miners. The question posed was whether the gasification experiment resulted in the increased migration of radon and thoron. If so, did it increase the radiation hazard to miners? The adaptation of the existing instrumentation to the specific conditions was conducted, and a series of measurements were made. It was found that the measured values of radon and thoron exhalation rates ranged from 3.0 up to 38 Bq·m-2·h-1 for radon and from 500 up to 2000 Bq·m-2·h-1 for thoron.

Radon Concentrations in Dwellings in the Mining Area-Are There Observed Effects of the Coal Mine Closure?

The article presents the results of radon research, carried out in the area of the mining commune in the Upper Silesian Coal Basin (USCB), Poland. Past investigations in the 1990s on radon concentrations in buildings, located within the mining area, showed that the indoor radon concentrations measured in the area affected by mining were higher than in buildings located outside that area. Currently, all underground hard coal mines within the boundaries of the observed commune have been closed. In 2020, after the closure of the last active mine, radon measurements were started again. The current results of indoor radon concentrations were compared with the archival results from the 1990s. It was found that the radon concentration increased significantly in the basements of buildings where measurements were made in 1990, 2020, and 2021: the maximum values were 260 Bq/m3, 644 Bq/m3, and 1041 Bq/m3, respectively. Therefore, these questions were posed: Do the mine closure processes increase radon migration? How long is the period of the occurrence of changes in radon concentrations in buildings after the cessation of mining operations?

Synthesis of xanthohumol and xanthohumol-d3 from naringenin.

A six-step synthesis of xanthohumol (1a) and its d3-derivative (1b) from easily accessible naringenin is reported. The prenyl side chain was introduced by Mitsunobu reaction followed by the europium-catalyzed Claisen rearrangement and base-mediated opening of chromanone gave access to an α,ß-conjugated ketone system. Compound 1b was used as an internal standard in stable isotope dilution assays of 1a in two Polish beers.

Long term behaviour of radium rich deposits in a lake ecosystem.

Behaviour of radionuclides released into environment is crucial for further evaluation of any kind of possible effects. Possibility of observation how does a radionuclide behave in natural environment is limited to very few post accidental areas. However, valuable observation can be collected at areas where enhanced concentration of natural radionuclides is presented caused by activity of non-nuclear industry. One example is area affected by release of radium rich brines from coal mines (Upper Silesia, south of Poland) that let one observe radium and its decay product behaviour in freshwater ecosystem from long-term perspective. Selected as long-term observatory site former mine water reservoir allowed identification of processes leading to accumulation of radium in bottom sediments and observation of its further behaviour from 17-years-time perspective. New data were collected during two-years monitoring campaign and compared with archive data on radioactivity in water and sediments collected in 1999. Radium-barium co-precipitation process was identified as main source of sediments heavy contamination, however, radium chemical form resulted from this process is insoluble and not easy migrate to other environmental compartments, what was proved by low 226Ra and 210Pb transfer to water measured under laboratory condition and to biota observed on site. As barium is not always present in mine radium rich brines a discussion is launched what would happen when such waters are released into environment based on simple laboratory experiment. In main conclusion is underlined that the current radium activity concentration in sediments is lower than expected only considering radioactive decay. Distribution of 226Ra, 228Ra and 210Pb in sediment profiles suggest that bio- or mechanical turbation (e.g. local flood) is responsible for significant 226Ra deficiency observed.

Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization.

Rational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often difficult due to limited information regarding the complete identification of a molecule's biological activities. The increasing affordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound's diverse effects on gene regulation. Here, we used an unbiased approach in lung and colon cancer cell lines to identify the early transcriptomic signatures of C-1305 cytotoxicity that highlight the novel pathways responsible for its biological activity. Our results demonstrate that C-1305 promotes direct microtubule stabilization as a part of its mechanism of action that leads to apoptosis. Furthermore, we show that C-1305 promotes G2 cell cycle arrest by modulating gene expression. The results indicate that C-1305 is the first microtubule stabilizing agent that also is a topoisomerase II inhibitor. This study provides a novel approach and methodology for delineating the antitumor mechanisms of other putative anticancer drug candidates.

Modelling of radon hazards in underground mine workings.

For many years, the legal regulations governing radiation protection were primarily concerned with artificial radioactivity, omitting in practice the hazards associated with the occurrence of natural radioactivity in non-nuclear industry. Meanwhile, materials with enhanced concentration of natural isotopes can pose serious radiation risks. A spectacular case is the hazard posed by short-lived radon progeny in underground mine workings. This hazard is significant even when radium isotope concentration in the rocks is at the natural level, and the main reason is relatively poor ventilation of mine workings. The current study contains a description of a developed model that includes a mathematical pattern of the ventilation network and possible radon sources. The model takes into account radon exhalation, generation of radon and its short-lived progeny, losses due to radioactive decay and diffusion of particles and their gravitational deposition; finally, it enables the estimation of doses to miners on the basis of recommended conversion factors. In addition the influence of size distributions of radioactive aerosols on dose conversion factors is discussed. To check and calibrate the model, measurements of radon concentration and potential alpha energy concentration of its decay progeny in an underground hard coal mine were performed during the mining operation.

Long term changes in the concentration of radium in discharge waters of coal mines and Upper Silesian rivers.

According to the latest guidelines of the International Atomic Energy Agency (IAEA, 2016), coal mining is one of the most important contributors to occupational exposure. Coal mining contributes about 45% of the total annual collective dose obtained by workers due to the exposure at places of working. One of the sources of exposure in mining are formation brines with elevated concentrations of natural radionuclides, the most common are radium 226Ra and 228Ra. Radium isotopes often occur in formation waters in underground collieries in the Upper Silesian region (USCB) in Poland. Significant amounts of radium remain underground in the form of radioactive deposits created as a result of spontaneous deposition or water treatment. This phenomenon leads to the increase of radiation hazard for miners. The remaining activities of 226Ra and 228Ra are released into the rivers with mine effluents, causing the contamination of bottom sediments and river banks. The results of radioactivity monitoring of effluents and river waters are presented here to illustrate a trend of long-term changes in environmental contamination, caused by mining industry in the Upper Silesian Region.

Oncogenic BRAF mutations and p16 expression in melanocytic nevi and melanoma in the Polish population.

INTRODUCTION: Twenty-five - fifty percent of skin melanomas arise from nevi. Melanocyte proliferation is activated by BRAFV600E, then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation. AIM: To analyze BRAFV600E, p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic melanoma in the Polish population. MATERIAL AND METHODS: One hundred and thirty-two nevi (dermal, compound, dysplastic) and 41 melanomas (in situ, primary, metastatic) were studied. BRAF was assessed by cobas® 4800 BRAFV600 Mutation Test, High Resolution Melting Assay validated with: pyrosequencing and immunohistochemistry. p16 and Ki67 expression was analyzed by IHC. RESULTS: Eighty-two percent of nevi and 57% of melanomas display BRAFV600E expression. Most dermal and compound nevi had > 50% of p16(+) cells. BRAFV600E dysplastic nevi had a low number of p16(+) cells. Nevi without BRAFV600E (WT), had 90% of cells p16(+). In 60% of in situ and primary melanomas, there was a low number of cells of p16(+). Fifty percent of WT metastatic melanoma and 33% of BRAFV600E showed a high level of p16. The number of Ki67(+) cells in dysplastic nevi was very low. In 25% of BRAFV600E melanomas in situ and 55% of WT, > 10% cells were Ki67(+). All BRAFV600E primary melanomas and 66% of WT had > 10% Ki67(+) cells. Twenty percent of BRAFV600E and WT metastases had > 10% of Ki67(+), however, 62% of BRAFV600E and 32% of WT samples had > 50% of Ki67(+) cells. CONCLUSIONS: BRAFV600E and p16 are more frequent in nevi than in melanoma in vivo. A significantly higher p16 expression was observed in mutated nevi than in WT, while in melanoma it was just the opposite. The proliferation rate of melanoma cells negatively correlated with p16 expression.

Febrile neutropenia in a metastatic melanoma patient treated with ipilimumab - case report.

BACKGROUND: Ipilimumab is a fully human monoclonal antibody (mAb) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab is currently approved in the U.S. and Europe for the treatment of metastatic melanoma in the first- and second-line treatment. Treatment with ipilimumab is linked to immune-related adverse events (irAEs) occurring in the majority of patients. These specific AEs include dermatitis, gastrointestinal disorders (diarrhea, colitis), hepatitis, hypophysitis, hypothyroidism, neuropathy, and iritis/inflammation of the ciliary body. CASE REPORT: We report a case of febrile neutropenia with agranulocytosis in the blood smear of a 35-year-old metastatic melanoma patient treated with ipilimumab 3 mg/kg. CONCLUSION: This AE was probably caused by antineutrophil antibodies associated with ipilimumab treatment. To our knowledge this is the first case report of febrile neutropenia in a metastatic melanoma patient treated with ipilimumab 3 mg/kg.

Skin pH is lower in type 1 diabetes subjects and is related to glycemic control of the disease.

BACKGROUND: Diabetes is a systemic disease affecting many organs, including skin. Skin may reflect the condition of internal organs. The aim of our study was to measure skin pH in type 1 diabetes mellitus (T1DM) patients and in healthy controls and to evaluate the association between metabolic control of diabetes and skin acidity in T1DM patients. MATERIALS AND METHODS: The study was conducted on 105 patients with T1DM and 53 age- and sex-matched healthy people. Skin surface pH was measured in three different areas of the body (cheek, forearm, and foot) in diabetes patients and healthy controls. The results were compared for patients' and controls' clinical characteristics and for patients' metabolic control and also evaluated according to the presence of complications of diabetes. RESULTS: Patients with T1DM had lower skin pH compared with the control group in three measured areas: within the cheek (5.49 ± 0.42 vs. 5.69 ± 0.31; P = 0.001), forearm (5.41 ± 0.46 vs. 5.73 ± 0.69; P = 0.004), and foot (5.20 ± 0.53 vs. 5.41 ± 0.41; P = 0.008). In the multiple linear regression skin pH was negatively correlated with fasting plasma glucose on the cheek (ß = -0.34, P = 0.0004), forearm (ß = -0.30, P = 0.0009), and foot (ß = -0.18, P = 0.04). Diabetes patients with glycated hemoglobin (HbA1c) ≥ 8% had significantly lower skin pH than patients with better glycemic control (HbA1c < 8%). However, we observed a statistically significant difference only on the foot (5.09 ± 0.50 vs. 5.34 ± 0.55; P = 0.019). CONCLUSIONS: Skin surface pH is lower in individuals with diabetes, and it is negatively related to actual and chronic hyperglycemia.

Resistance to vemurafenib can be reversible after treatment interruption: a case report of a metastatic melanoma patient.

About 40% to 60% of melanomas present BRAF mutation. Selective BRAF inhibitors such as vemurafenib and dabrafenib are currently approved for the treatment of advanced melanoma patients with BRAF mutation. The treatment-induced tumor regression occurs in the majority of patients; however, acquired resistance to BRAF inhibitors is observed in most of the patients after 6 to 7 months. After progression of the disease, the patient might be offered treatment with ipilimumab followed by chemotherapy. Subsequent lines of systemic treatment of metastatic melanoma patients do not exist.Here we report a case of a 59-year-old woman with a diagnosis of BRAF-mutant metastatic melanoma that responded to initial treatment with vemurafenib. Subsequently, after disease progression, the patient received chemotherapy. Since no clinical response to dacarbazine was observed, carboplatin with paclitaxel were applied. Transient partial response was obtained, which was followed by further disease progression. Then retreatment with vemurafenib was applied. The patient developed very short-term tumor regression and significant biochemical response (serum lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) to the treatment. However, following 5 weeks of retreatment, the patient developed progression of the disease. Our clinical observation indicates that in melanoma patients who developed resistance to selective BRAF inhibitors, rechallenge after treatment interruption might be beneficial.

Acne inversa goes an extra mile than hidradenitis suppurativa.

Acne inversa (AI, hidradenitis suppurativa, Velpeau's disease, Verneuil's disease) is a severe, chronic inflammatory dermatosis of unknown etiology, detected on the basis of clinical symptoms more frequently in women than in men. Purulent lesions in the form of nodules and inflammatory tumors, fistulas and scars are present in the areas with hair follicles and apocrine glands, most commonly on the armpits, groin, around the anus and pubic region. Acne inversa can lead to physical and mental disorders. Unfortunately, it is often misdiagnosed and ineffectively treated. The paper presents a case of a 46-year-old patient who was successfully treated surgically for AI around the anus and buttocks by excision of the changes and closure of the wound with local flaps and split-thickness skin grafts, taken with dermatome from the rear surface of the thighs. Surgical treatment is the method of choice in the treatment of severe AI.

Application of zeolites for radium removal from mine water.

For removal of radium from saline waters in Upper Silesian mines, several methods of purification have been developed. The most efficient one is based on application of barium chloride, which was implemented in full technical scale in two Polish coal mines several years ago. Very good results of purification have been achieved-the removal efficiency exceeding 95% of the initial activity. Another possibility for the removal of different ions from salty waters and brines is the application of zeolites. We found that technique as a very promising method for removal of not only radium isotopes from mine waters but also other ions (barium, iron, manganese). Treatment of several various water samples has been done to assess the removal efficiency for natural radionuclides. Preliminary results show very good effects for radium isotopes as well as for barium ions. In the paper, a short description of laboratory results of the purification of mine waters with application of synthetic zeolites is presented.

New therapeutic options in systemic treatment of advanced cutaneous melanoma.

INTRODUCTION: For many years systemic treatment of advanced/metastatic melanoma has been based on chemotherapy or immunotherapy. However, even very toxic regimens (e.g., polychemotherapy, bio-chemotherapy or immunotherapy with HD-IL-2) despite increased response rates as compared with standard dacarbazine monotherapy have not improved patients' outcomes. Over the last two decades, a huge effort, made in order to determine the molecular and immunological mechanisms responsible for biology of melanoma led to development of novel targeted agents. AREAS COVERED: The aim of this article is to summarize data on novel targeted agents used for treatment of metastatic melanoma. The authors searched PubMed, EMBASE and abstracts from ASCO, ESMO, AACR congresses for Phase II/III clinical studies evaluating novel immunomodulating agents and kinase inhibitors in melanoma patients. EXPERT OPINION: Elucidation of the crucial role of MAPK pathway and BRAF kinase mutations in particular has led to development of specific small molecule kinase inhibitors (vemurafenib, dabrafenib, trametinib), and new insight into molecular mechanisms responsible for immune response and tolerance resulted in development of immunomodulatory agents (ipilimumab, anti-PD1, anti-PD-L1). The introduction of novel drugs has changed the natural history of melanoma. However, it has also generated new clinical challenges that have to be resolved as soon as possible.

Basal cell carcinoma - diagnosis.

Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate.

Co-occurrence of acanthosis nigricans and bladder adenocarcinoma - case report.

Acanthosis nigricans (AN) is characterized by the occurrence of symmetrical velvety hyperpigmented plaques that can be observed in each location on the skin. However, the lesions are most frequently located in the axillary, inguinal and nuchal areas. Primarily, the lesions appear as hyperpigmented focuses which later transform into papillary lesions. There are two forms of the disease - benign and malignant. Malignant AN is considered to represent paraneoplastic syndrome co-occurring with advanced cancer, but as such it is not malignant. This article presents a case of a patient diagnosed with AN and coexisting bladder cancer and discusses the case in the context of available literature.

Progress in the treatment of bone metastases in cancer patients.

INTRODUCTION: Bone metastases are a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. Skeletal-related events involving pathological fractures, spinal cord compression and a need for surgery/radiotherapy, which are frequently observed in cancer patients with bone metastases have a detrimental effect on patients' survival and quality of life. Therefore, prevention of skeletal-related events is a crucial element in cancer treatment. AREAS COVERED: The aim of this article was to summarize data on bone-modifying agents used for treatment of cancer patients with bone metastases. We searched PubMed, EMBASE, and abstracts from ASCO, AUA, ESMO, AACR congresses for clinical studies evaluating bone-modulating agents in the treatment of patients with bone metastases. EXPERT OPINION: In breast cancer patients with bone metastasis, several bisphosphonates and denosumab demonstrated clinical efficacy. On the other hand, in patients with bone metastases from prostate cancer or other solid tumors only zoledronic acid and denosumab were clinically active. However, neither bisphosphonates nor denosumab have any positive impact on survival of patients with bone metastases. In a recent interim analysis of a Phase III clinical study, a novel bone-modulating agent - radium-223 chloride (alpharadin), a bone-seeking alpha emitter, has been demonstrated to significantly improve median overall survival of prostate cancer patients with bone metastases compared with placebo.

Mean annual (222)Rn concentration in homes located in different geological regions of Poland: first approach to whole country area.

The paper presents the results of year-long measurements of radon ((222)Rn) concentration inside 129 buildings in Poland in relation to the geological conditions of their foundation. The authors took into account the division of the country into tectonic units, as well as the lithology of the rocks forming the bedrock of these buildings. As expected, the highest value of mean annual (222)Rn concentration (845 Bq/m(3)) was recorded in a building situated in the area of the Sudetes, while the highest geometric mean (characteristic of the expected log-normal data distribution) was calculated based on measurements from buildings located within the East-European craton, in the area of Mazury-Podlasie monocline, where it reached 231 Bq/m(3). Such results reflect geological conditions - the occurrence of crystalline rocks (especially U- and Ra-enriched granites and orthogneisses) on the surface in the Sudetes, and of young post-glacial sediments containing fragments of Scandinavian crystalline rocks, also enriched with U and Ra, in the area of Mazury-Podlasie monocline. However, the least expected result of the investigations was finding out that, contrary to the hitherto widespread belief, none of the major tectonic units of Poland can be excluded from the list of those containing buildings with mean annual (222)Rn concentration exceeding 200 Bq/m(3). The mean annual concentration of radon for all the buildings were much higher than the mean concentration value (49.1 Bq/m(3)) of indoor radon in Poland quoted so far. These results cast a completely new light on the necessity to perform measurements of radon concentration in residential buildings in Poland, no more with reference to small areas with outcrops of crystalline rocks (especially the Sudetes, being the Polish fragment of the European Variscan belt), but for all the major tectonic units within Poland.