Corrections of HPGe detector efficiency curve due to true coincidence summing by program EFFTRAN and by Monte Carlo simulations.

Standard reference sources, used for efficiency curve calibration of detector, often contain radionuclides with complex decay schemes (such as 60Co, 88Y, 152Eu …), introducing a potential problem in gamma-ray spectrometry, due to the appearance of coincidence summing of detected photons, in particular at a low source-detector distance. In this paper, a set of Monte Carlo simulations of an identical experimental setup were performed in order to obtain the efficiency curve of coaxial p-type HPGe detector for energy region (0-2) MeV, with the effect of true coincidence summing and without it. Obtained efficiency curves are compared with the experimental curve after applied EFFTRAN corrections. Fairly well agreement (between simulated and experimental curves with EFFTRAN corrections (with a relative deviation of 10%) proved the reliability of EFFTRAN corrections, as well as the possibility of Monte Carlo simulations for efficiency curve determination.

The COVID-19 pandemic - related psychological distress and job burnout among Serbian pharmacy practitioners: a cross-sectional online study.

OBJECTIVE: The current COVID-19 pandemic has increased occupational stress for all healthcare providers, making job burnout one of the most common and largely unrecognized mental health issues among healthcare professionals. Besides physicians and nurses, pharmacy practitioners were "front-line" healthcare professionals with a critical and unique role in the public health crisis. Considering this, the aim of this study was to examine distress levels and the prevalence of job burnout among Serbian pharmacy practitioners in relation to the COVID-19 pandemic. SUBJECTS AND METHODS: This cross-sectional online study was conducted in April and May of 2020. A total of 176 pharmacy practitioners anonymously and voluntarily completed the two-section questionnaire, consisting of Copenhagen burnout inventory, CBI and 4DSQ Distress subscale. The two-section questionnaire was distributed online, among various social-media groups of pharmacy practitioners, as well as by personal contacts following the "snowball" sampling method. RESULTS: Results revealed moderately high burnout scores in our sample. The majority of the participants showed signs of personal-related job burnout, followed by work-related and client-related burnout. A strongly elevated distress level was obtained in almost two-thirds of study respondents. In addition, a significant and high correlation of all CBI subscales with distress was found, as well as medium correlations with sleep duration shortening as a mediator between distress and job burnout. CONCLUSIONS: Results of our study showed that job burnout significantly increased among pharmacy practitioners during the COVID-19 pandemic. Furthermore, we discovered that stress has an indirect impact on study participants' burnout via insufficient sleep.

Estimation of absorbed gamma dose rate from granite by Monte Carlo simulation approach.

Apart from the continuous exposure of humans to background ionising radiation, an increased level of radiation may also originate from the use of building materials with an enhanced level of radioactivity. Thus, it is necessary to examine the content of radionuclides present in building materials, as well as the corresponding dose which may be received by residents from these materials. In this paper, particular attention was dedicated to finding the absorbed dose rate and annual effective dose caused by the presence of naturally occurring radioisotopes 226Ra, 232Th, and 40K in granite, a widely used building material, by means of Monte Carlo simulations. In addition, the obtained dose rate simulation results were compared with values estimated from commonly used simple equations, relating to the dose rate emitted by granite plates, covering the interior of a standard room. In the simulation, a room was constructed with standard dimensions (4 m × 5 m × 2.8 m), and with floor and walls covered with 3 cm thick granite. A water cylinder (approximate mass 65 kg) was positioned in the center of the room, representing a human body. The emission of the most intense gamma rays from 226Ra and 232Th progenies, as well as from 40K, emanating from the granite matrix, was simulated. The number of generated photons in each simulation (typically it was an order of magnitude of ~106) precisely represented actual activity concentrations of 226Ra, 232Th, and 40K in granite samples. All processes playing a role in the interactions of gamma photons with the granite matrix itself, the outer concrete shell, the air within the room, and the water cylinder, were taken into account by GEANT4 simulation software, after which the spectra of deposited energy inside of the water cylinder were obtained. Based on the deposited energy, the absorbed dose rate and annual effective dose were calculated for 6 analysed granite samples, each with different 226Ra, 232Th, and 40K contents. Furthermore, the effect of the position of the water cylinder in the simulated room on the absorbed dose rate was considered, as well as the distribution of the deposited energy within the water cylinder. The absorbed dose rates, and consequently annual effective dose, obtained in the simulations were found to be 30%-40% higher than the values obtained from using a standard formula.

Simple coincidence technique for cosmic-ray intensity exploration via low-energy photon detection.

Changes in cosmic-ray intensity can significantly influence the search for rare events or processes in nuclear and astroparticle physics through corresponding variations in detector background count rate. In this work, we present an approach to explore cosmic-ray intensity and corresponding cascade production of secondary particles in the detector vicinity using low-energy photon background spectra induced by cosmic rays at the earth's surface. The coincidence system based on a plastic scintillator and an extended range HPGe detector, including a multiparameter device, was used for the acquisition of low-energy photon spectra. This system was also simulated by the GEANT4 toolkit, and the simulated and experimental spectra were compared. Single aperiodic events, as well as possible periodic behavior of low-energy photon emission were searched for.

Monte Carlo simulation of beta particle-induced bremsstrahlung doses.

It is well known that protection from the external irradiation produced by beta emitters is simpler than the corresponding shielding of radioactive sources that emit gamma radiation. This is caused by the relatively strong absorption (i.e. short range) of electrons in different materials. However, for strong beta sources specific attention should be paid to the bremsstrahlung radiation induced in the source encapsulation (matrix), especially for emitters with relatively high beta-endpoint energy (1 MeV) that are frequently used in nuclear medicine. In the present work, the bremsstrahlung spectra produced in various materials by the following beta emitters, Sr-90 (together with its daughter Y-90), P-32 and Bi-210, were investigated by Monte Carlo simulations using Geant4 software. In these simulations, it is supposed that the point radioactive sources are surrounded by cylindrically shaped capsules made from different materials: Pb, Cu, Al, glass and plastic. For the case of Y-90(Sr-90) in cylindrical lead and aluminum capsules, the dimensions of these capsules have also been varied. The absorbed dose rates from bremsstrahlung radiation were calculated for cases where the encapsulated point source is placed at a distance of 30 mm from the surface of a water cylinder with a mass of 75 kg (approximately representing the human body). The bremsstrahlung dose rate and bremsstrahlung spectrum from the Y-90(Sr-90) point source encapsulated in an Al capsule were also measured experimentally and compared with the corresponding simulation results. In addition, the bremsstrahlung radiation risk for medical staff in therapies using Y-90 was considered in simulations, relating to finger dose as well as whole-body dose during preparation and injection of this radioisotope. The corresponding annual doses were obtained for medical workers for specified numbers of Y-90 applications to patients.

Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential.

Claudin-low tumors are a highly aggressive breast cancer subtype with no targeted treatments and a clinically documented resistance to chemotherapy. They are significantly enriched in cancer stem cells (CSCs), which makes claudin-low tumor models particularly attractive for studying CSC behavior and developing novel approaches to minimize CSC therapy resistance. One proposed mechanism by which CSCs arise is via an epithelial-mesenchymal transition (EMT), and reversal of this process may provide a potential therapeutic approach for increasing tumor chemosensitivity. Therefore, we investigated the role of known EMT regulators, miR-200 family of microRNAs in controlling the epithelial state, stem-like properties and therapeutic response in an in vivo primary, syngeneic p53(null) claudin-low tumor model that is normally deficient in miR-200 expression. Using an inducible lentiviral approach, we expressed the miR-200c cluster in this model and found that it changed the epithelial state, and consequently, impeded CSC behavior in these mesenchymal tumors. Moreover, these state changes were accompanied by a decrease in proliferation and an increase in the differentiation status. miR-200c expression also forced a significant reorganization of tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion and motility. Accordingly, induced miR200c expression significantly enhanced the chemosensitivity and decreased the metastatic potential of this p53(null) claudin-low tumor model. Collectively, our data suggest that miR-200c expression in claudin-low tumors offers a potential therapeutic application to disrupt the EMT program on multiple fronts in this mesenchymal tumor subtype, by altering tumor growth, chemosensitivity and metastatic potential in vivo.

Single nucleotide polymorphism in the interleukin 12B gene is associated with risk for breast cancer development.

We analysed the association of a single nucleotide polymorphism (SNP) in the gene encoding the IL-12 subunit p40 (IL12B, rs3212227, A>C) with breast cancer. The SNPs allelic and genotypic frequencies were compared between patients (n = 191) and healthy (n = 194) women in a case-control study from Croatia. The major allele (A) was associated with susceptibility to breast cancer (P = 0.003; OR = 1.67; 95% CI: 1.17-2.38). Likewise, the minor allele (C) was significantly correlated with protection (P = 0.003; OR = 0.60; 95% CI: 0.42-0.86). At the genotype level, AA homozygosity was significantly associated with predisposition to disease (P = 0.013; OR = 1.68, 95% CI: 1.09-2.59), whereas the minor allele homozygosity (CC) was correlated with protection to disease (P = 0.020, OR = 0.28, 95% CI: 0.09-0.91). The heterozygous genotype showed no significant correlation with disease. The product of the IL12B gene (IL-12 p40) can either form a homodimeric cytokine or be part of two pro-inflammatory (IL-12 and IL-23) cytokines. It is presently unclear whether the major allele is associated with higher or lower protein levels of IL-12 p40 and IL-12 p70, which are critical in inflammation and adaptive immune responses. However, as the A allele is high producer of IL12B (p40) mRNA, these results might imply that higher levels of IL-12 p40 (either as homodimers or joined with one or both of the other two subunits) predispose to breast cancer.

Toll-like receptor 2 (P631H) mutant impairs membrane internalization and is a dominant negative allele.

We have sequenced 416 Toll-like receptor-2 (TLR2) alleles in 208 subjects in a tuberculosis case-control study in Croatian Caucasian population. We found ten single nucleotide polymorphisms (SNP) among which three were novel (S97S, T138I and L266F). The genotype containing TLR2-P631H SNP was significantly overrepresented in patients with tuberculosis when compared to contact controls, suggesting a small yet increased risk to disease. The causative agent of tuberculosis is Mycobacterium tuberculosis, which can bind to TLR2 with its lipoprotein coat. The TLR2-P631H mutant has a dominant negative effect on the wild type TLR2 signalling in transfected HEK293 kidney cells using the NF-kappaB-driven luciferase as a reporter gene with ligands like M. avium extracts, Pam3CysSK4 or FSL-1 that bind TLR2/TLR1 or TLR2/TLR6 heterodimers, respectively. Studies on internalization from the Regular Madine Darby Canine Kidney cell surface into the early endosomal compartments showed a lower rate of the mutant compared to the wild type. Our data, in combination with a report by others show that the TLR2-P631H allele could be associated with protection to meningococcal meningitis, suggest that by dominantly inhibiting the response of cells important in the immune response this mutant might confer either protection or susceptibility to meningitis or tuberculosis, respectively.

Induced sputum in systemic sclerosis interstitial lung disease: comparison to healthy controls and bronchoalveolar lavage.

BACKGROUND: Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. OBJECTIVE: To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV(1)), FEV(1)/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. RESULTS: The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 +/- 23.89 vs. 27.37 +/- 17.90), as well as lymphocytes (17.42 +/- 19.70 vs. 3.13 +/- 2.28) and eosinophils (2.35 +/- 4.43 vs. 0.41 +/- 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 +/- 19.15 vs. 36.96 +/- 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% +/- 17.26), while neutrophils (14.77 +/- 17.18%) and lymphocytes (15.62 +/- 13.46%) were less frequent and eosinophils (1.66 +/- 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 +/- 21.67% of macrophages, 39.72 +/- 23.15% of neutrophils, 15.28 +/- 19.46% of lymphocytes and 2.56 +/- 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV(1) (mean value before IS was 85.09 +/- 14.44 and 88.93 +/- 16.40 after IS) and FEV(1)/forced vital capacity (mean value before IS was 98.53 +/- 12.11 and 105.22 +/- 10.78 after IS) was observed. CONCLUSION: The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.

Colon interposition in the treatment of esophageal caustic strictures: 40 years of experience.

The objective of this article was to analyze 40 years of experience of colon interposition in the surgical treatment of caustic esophageal strictures from the standpoints of our long-term personal experience. Colon interposition has proved to be the most suitable type of reconstruction for esophageal corrosive strictures. The choice of colon graft is based on the pattern of blood supply, while the type of anastomosis is determined by the stricture level and the part of colon used for reconstruction. In the period between 1964 and 2004, colon interposition was performed in 336 patients with a corrosively scared esophagus, using the left colon in 76.78% of the patients. In 87.5% a colon interposition was performed, while in the remaining patients an additional esophagectomy with colon interposition had to be done. Hypopharyngeal strictures were present in 24.10% of the patients. Long-term follow-up results were obtained in the period between 1 to up to 30 years. Early postoperative complications occurred in 26.48% of patients, among which anastomosic leakage was the most common. The operative mortality rate was 4.16% and late postoperative complications were present in 13.99% of the patients. A long-term follow up obtained in 84.82% of the patients found excellent functional results in 75.89% of them. We conclude that a colon graft is an excellent esophageal substitute for patients with esophageal corrosive strictures, and when used by experienced surgical teams it provides a low rate of postoperative morbidity and mortality, and long-term good and functional quality of life.

Interferon-gamma gene (T874A and G2109A) polymorphisms are associated with microscopy-positive tuberculosis.

Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon-gamma (IFN-gamma) gene IFNG T+874A and IFNG G+2109A correlate with the IFN-gamma production in vitro, and the frequency of potential high IFN-gamma producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-gamma gene and predisposition to tuberculosis. We analysed two IFNG SNPs (T+874A and G+2109A) in patients (n = 253) hospitalized in Rijeka (Croatia) and controls (n = 519) from the same area. One-fifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/T+874 (possible high IFN-gamma producer) and +874A/A (putative low producer) genotypes were associated with microscopically positive-negative forms of disease. Haplotypes (T+874A and G+2109A) based on a prediction by software phase and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at +874 (AA/AA; AA/AG and AG/AG) in microscopy- or bacterial culture-positive groups compared with their negative counterparts. These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.

Interferon-gamma receptor-1 gene promoter polymorphisms (G-611A; T-56C) and susceptibility to tuberculosis.

We analysed frequencies of two single-nucleotide polymorphisms (SNP) in the interferon-gamma (IFN-gamma) receptor-1 (IFNGR1) gene promoter (G-611A, T-56C) in tuberculosis patients (n = 244) and compared them with controls (n = 521). These frequencies were not significantly different, whether analysed independently or as haplotypes. Because these SNP affect transcription, the results suggest that the expression of the IFNGR1 gene does not confer susceptibility to disease in patients from Croatia. Further analysis revealed a significant association between the protective (CA)(n) polymorphism (22 repeats, 192 FA(1)), located in the fifth intron of the IFNGR1 gene (+16682), and GT promoter haplotype (-611; -56) that showed the strongest expression capacity. In addition to this cis relationship, the (CA)(22) allele was correlated in trans with an IFN-gamma SNP (IFNG G + 2109A), which might affect the transcription of the IFNG gene. These results suggest that a particular combination of IFNG and IFNGR1 SNP might offer a better protection against tuberculosis in this population.

Beta-cell secretory function and CD25 + lymphocyte subsets in the early stage of type 1 diabetes mellitus.

Cellular immunologic tests have not been used for diagnostic purposes in individuals at risk for autoimmune insulitis or in patients with partial beta-cell destruction because of a lack of studies that show their predictive value. In this study we initially evaluated 43 patients with recent-onset Type 1 diabetes (disease duration

Interferon-gamma receptor-1 gene polymorphism in tuberculosis patients from Croatia.

Recent studies have indicated that the interleukin-12/interferon-gamma (IFN-gamma) axis is important in mycobacterial infection susceptibility. Using an intronic (CA)n polymorphic microsatellite marker within the IFN-gamma receptor-1 (IFNGR1) gene, we have compared the allelic frequencies of this marker in hospitalized tuberculosis patients (n = 120) with that of controls (n = 87) from Rijeka, Croatia. We identified 13 (CA)n alleles in the tuberculosis patients, whereas only 10 were found in the controls. A significant difference between one allelic marker and the control group was observed (P = 0.02, 95% confidence interval 0.14-0.94), suggesting a possible protective association. In contrast, several other allelic markers showed a trend towards association with the disease. We also found a trend towards an increased frequency in homozygosity of one allelic marker in patients (11.7%) as compared with controls (4.6%). We conclude that there is no evidence for disease association of the IFNGR1 gene marker in Mendelian-type (single-allele) inheritance. However, our results also suggest that unidentified allelic variations in the IFNGR1 gene might elevate or decrease the risk in this ethnic population, as a part of the multigenic predisposition to tuberculosis.

Isolated choroidal metastasis from primary adenocarcinoma of the distal esophagus: a case report.

We present a case of a 41-year-old male patient who, 1 year after transhiatal esophagectomy and transmediastinal gastroplasty for an adenocarcinoma of the distal esophagus, presented with an isolated metastasis in the choroids of the left eye. Because of pains caused by secondary glaucoma, enucleation of the left eyeball had to be performed as the treatment of choice. At 1 year after surgery of the eye, the secondaries in both adrenal glands were revealed. Despite the applied chemotherapy, the patient died with signs of generalized disease 3 years after the initial surgery.

[History of the evolution of surgical treatment of gastroesophageal reflux disease]. / Istorijska evolucija hirurskog lecenja gastroezofagealne refluksne bolesti.

The GERD has probably existed since the beginning of mankind but it took several millennia since any perception or knowledge of this disease started to evolve. Homo est quod est--the man is what he eats is an old Latin proverb and heartburn has been one of the most common documented symptoms in humans in the last two centuries. The term peptic esophagitis has been introduced in 1935, but the evolution of knowledge of pathogenesis, incidence, complications and way of treatment of GERD has been quite slow. In the last decade several new aspects of these problem have evolved and probably explained many unanswered questions of this very common and sometimes severe disease.

[Surgical management of long-term complications after dermatojejunoplasty of corrosive esophageal strictures]. / Hirursko lecenje kasnih komplikacija dermato-jejuno plastika kod korozivnih stenoza jednjaka.

Authors present their experience in treatment of the long term complications after Lexer-Judin and Lexer-Judin-Papo operations. They discuss the advantages and disadvantages of these procedures. In the period from 1977 to 2003 in the Institute for digestive diseases 16 patients had to be operated because of the stenosis in the region of dermato-jejunal anastomosis or because of the bad esthetic results of this operations. They suggest that the extirpation of dermal tube, mobilisation of the jejunum and new pharyngo-jejunal anastomosis is the operation of choice.

[Correction of failed primary surgical interventions in benign lesions of the esophagus]. / Korekcija neuspelih primarnih hirurskih intervencija kod benignih lezija jednjaka.

In an retrospective analysis of documentation and printed paper in period between 1964-1998 168 patients required reoperations in benign esophageal lesions. Failed initial interventions were found in 66 (39.28%) pts. operated in our clinic and 102 (60.71%) pts operated in other institutions in our country. The corrective procedure was possible in 140 (83.33%) pts and impossible in 11 (6.54%). Post-operative mortality was 7.73% so the definitive failed corrections were 14.27%. The main cause of failure were: Defective operative technique, wrong preoperative diagnosis and indications including inadequate initial procedure. Among the 168 pts undergoing corrective surgery, more than a half of pts had obstructive lesions requiring resections and reconstructions. Dilatation of the stricture was possible in 16% followed by total diversion, particularly in previous gastric surgery. Malignant degeneration of benign lesions were found in 10.71%. Only 4 pts (2.3%) refused suggested operations. Satisfactory long-term results especially in patients undergoing esophageal corrective reconstructions for benign diseases were good to excellent in regular yearly postoperative routine control examination.

[Esophagus preserving surgery--eversion and mucosal stripping]. / Postedna hirurgija jednjaka--everzioni i mukozni stripping.

The eversional stripping and esophageal mucosal stripping methods as standard procedures in the preserving esophageal surgery are presented in this paper. These procedures have indication limit and results are excellent in selected risk dependent group of patients. This review describes technique, indications and advantages of these techniques in comparision with conventional finger esophageal dissection.

[Surgical treatment of cardial carcinoma]. / Hirursko lecenje karcinoma kardije.

In the period from 1970 to 1996, in the Departmenf of Esophagogastric Surgery, Belgrade, Yugoslavia 562 have been operated with curative intent due to cardiac carcinoma. Since 1970 until 1985, in 182 patients a distal esophagectomy and proximal gastrectomy followed by eosphagogastro anastomosis had been performed. In the period between 1982 and 1996, a distal esophagectomy with total gastrectomy and radical or extended radical dissection and intrathoracic esophagojejuno anastomosis in 380 patients (192 hand sewn 3/0 interrupted sutures and 188 spapled anastomosis) had been performed. In our opinion for the majority of patients with advanced cardiac carcinoma distal esophagectomy and total gastrectomy, via the left thoracoabdominal approach, with D2 pancreas preserving splenectomy and dissection of lymph nodes in stations 16a1 and 16a2 is a surgical therapy of choice. Overall complications of such a procedure not differ in type and number from those after standard total gastrectomy and D2 dissection.