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Mossbauer spectroscopy and radiotracer analysis of the influence of evaporated aluminium layer gettering on cast multicrystalline and single crystalline radioactive cobalt-57-doped silicon reveal that Al gettering is operational at high temperatures and transports the cobalt atoms in Si bulk to the liquid A1-Si phase. The metallic impurity in the liquid Al-Si phase has a high solubility that enables the elucidation of Al gettering as a segregation mechanism.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies., Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors., Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio., Exposure: Preoperative S aureus colonization., Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models., Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs., Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

ATP-binding cassette (ABC) drug efflux transporters and drug metabolizing enzymes play crucial roles in pharmacokinetic drug-drug interactions and multidrug tumor resistance (MDR). Tazemetostat (EPZ-6438, Tazverik) is a novel epigenetic drug that has been recently approved for the therapy of advanced epithelioid sarcoma and follicular lymphoma. Additionally, this medication is currently being clinically tested to treat several other cancers such as non-small cell lung cancer (NSCLC). This study aimed to investigate the inhibitory effects of tazemetostat on selected ABC transporters/cytochrome P450 3A4 (CYP3A4) enzyme to comprehensively explore its role in MDR. First, our accumulation and molecular docking studies showed that tazemetostat is a unique triple inhibitor of ABCB1, ABCC1, and ABCG2 transporters. In contrast, tazemetostat exhibited only low level of interaction with the CYP3A4 isozyme. Drug combination assays confirmed that tazemetostat is a multipotent MDR modulator able to synergize with various conventional chemotherapeutics in vitro. Subsequent caspase activity assays and microscopic staining of apoptotic nuclei proved that the effective induction of apoptosis is behind the observed synergies. Notably, a potent MDR-modulatory capacity of tazemetostat was recorded in primary ex vivo NSCLC explants generated from patients' biopsies. On the contrary, its possible position of pharmacokinetic MDR's victim was excluded in comparative proliferation assays. Finally, tested drug has not been identified as an inducer of resistant phenotype in NSCLC cell lines. In conclusion, we demonstrated that tazemetostat is a unique multispecific chemosensitizer, which has strong potential to overcome limitations seen in the era of traditional MDR modulators., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Postoperative chylothorax is a well-known rare complication of thoracic surgery. It is a serious complication that is fatal in cases of inadequate treatment. The authors present 2 cases of postoperative chylothorax that were successfully treated by performing pedal and/or intranodal lymphography. In one case, the patient underwent lymphography after previous unsuccessful surgical ligation of the thoracic duct. The presented case reports describe therapeutic importance of conventional lymphography as a minimally invasive treatment of the postoperative chylothorax.

The authors present a case of a patient with non-traumatic right-sided chylothorax which was successfully treated by thoracic duct embolization. The procedure was performed through the cisterna chyli which was visualised by intranodal lymphography. The coils and acrylic tissue glues were used for embolization. The patient has been followed for 5 months and is free of recurrence of chylothorax.

Encorafenib (LGX818, trade name Braftovi), a novel BRAF inhibitor, has been approved for the treatment of melanoma and colorectal cancer. In the present work, we evaluated encorafenib's possible antagonistic effects on the pharmacokinetic mechanisms of multidrug resistance (MDR), as well as its perpetrator role in drug interactions. Firstly, encorafenib potently inhibited the efflux function of the ABCC1 transporter in drug accumulation assays, while moderate and null interaction levels were recorded for ABCB1 and ABCG2, respectively. In contrast, the mRNA expression levels of all the tested transporters were not altered by encorafenib. In the drug combination studies, we found that daunorubicin and topotecan resistances were synergistically attenuated by the encorafenib-mediated interaction in A431-ABCC1 cells. Notably, further experiments in ex vivo patient-derived explants confirmed the MDR-modulating ability of encorafenib. Advantageously, the overexpression of tested drug efflux transporters failed to hinder the antiproliferative activity of encorafenib. In addition, no significant modulation of the CYP3A4 enzyme's activity by encorafenib was observed. In conclusion, our work indicated that encorafenib can act as an effective chemosensitizer targeting the ABCC1-induced MDR. Our in vitro and ex vivo data might provide valuable information for designing the novel effective scheme applicable in the clinical pharmacotherapy of BRAF -mutated/ABCC1-expressing tumors., Competing Interests: The authors declare no conflict of interest.

Talazoparib (Talzenna) is a novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor that is clinically used for the therapy of breast cancer. Furthermore, the drug has shown antitumor activity against different cancer types, including non-small cell lung cancer (NSCLC). In this work, we investigated the possible inhibitory interactions of talazoparib toward selected ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 biotransformation enzymes (CYPs) and evaluated its position in multidrug resistance (MDR). In accumulation studies, talazoparib interacted with the ABCC1 and ABCG2 transporters, but there were no significant effects on ABCB1. Furthermore, incubation assays revealed a negligible capacity of the tested drug to inhibit clinically relevant CYPs. In in vitro drug combination experiments, talazoparib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCC1 and ABCG2 expression, respectively. Importantly, the position of an effective MDR modulator was further confirmed in drug combinations performed in ex vivo NSCLC patients-derived explants, whereas the possible victim role was refuted in comparative proliferation experiments. In addition, talazoparib had no significant effects on the mRNA-level expressions of MDR-related ABC transporters in the MCF-7 cellular model. In summary, our study presents a comprehensive overview on the pharmacokinetic drug-drug interactions (DDI) profile of talazoparib. Moreover, we introduced talazoparib as an efficient MDR antagonist.

Sonidegib (LDE-225) is a Hedgehog pathway inhibitor used for the therapy of basal cell carcinoma. In addition, the drug is a subject of clinical trials for the treatment of other solid tumors including non-small cell lung cancer (NSCLC). In this study, we explored the potential of sonidegib to act as a perpetrator of drug-drug interactions (DDIs) and modulator of transporter- and enzyme-mediated multidrug resistance (MDR). First, we found that transport functions of ABCB1 and ABCG2 were effectively inhibited by sonidegib in accumulation studies. In contrast, the drug did not cause fluctuations in mRNA levels of tested efflux transporters. In drug combination assays, sonidegib synergistically enhanced the cytotoxicity of daunorubicin and mitoxantrone in ABCB1- and ABCG2-overexpressing cells, respectively. Notably, similar phenomena were also observed in explant tumor cultures derived from NSCLC-suffering patients. In addition, the anticancer effects of sonidegib were not hampered by the expression of the ABC transporters associated with MDR. Last, sonidegib had no significant influence on the activity of CYP3A4 isoform in vitro. In summary, our work suggests that sonidegib can be considered a potential perpetrator of clinical DDIs on ABCB1 and ABCG2. After in vivo evaluation, its chemosensitizing properties might be projected into efficient and safe treatment regimen for the clinical management of NSCLC patients with high ABCB1/ABCG2 expression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Primary cardiac tumors are a rare condition presenting with a variety of symptoms. The outcomes of their surgical treatment in the modern era from central Europe have not been recently reported., Aim: To evaluate the short- and long-term outcomes of the cardiac tumor operations at our department throughout the last 20 years., Material and Methods: This was a retrospective analysis of all primary cardiac tumor operations performed at our institution between 2000 and 2020. Perioperative data were extracted from patient records. Long-term data were provided by the National Registry of Cardiac Surgery., Results: Sixty procedures for primary cardiac tumor were performed throughout the study period. The most common type of tumor was myxoma (88%), followed by fibroelastoma (8%), lipoma (2%) and sarcoma (2%). There were 2 perioperative deaths (3%). The most common perioperative complication was atrial fibrillation (47%). One (2%) patient underwent reoperation 6 years later because of myxoma recurrence. We recorded 13 long-term deaths, but only 1 patient died as a consequence of cardiac tumor (sarcoma) 15 months after the surgery. Long-term survival of the cohort was comparable with the age- and sex-matched general population up to 15 years postoperatively (relative survival 0.91, CI 0.68-1.23). Rich histopathological illustrations are provided in the online supplementary material., Conclusions: Surgical resection is the standard treatment of primary cardiac tumors. The outcomes of benign tumors are excellent and the long-term postoperative survival is comparable with the general population. The prognosis of malignant tumors remains poor., Competing Interests: The authors report no conflict of interest., (Copyright: © 2022 Polish Society of Cardiothoracic Surgeons (Polskie Towarzystwo KardioTorakochirurgów) and the editors of the Polish Journal of Cardio-Thoracic Surgery (Kardiochirurgia i Torakochirurgia Polska).)

Tepotinib is a novel tyrosine kinase inhibitor recently approved for the treatment of non-small cell lung cancer (NSCLC). In this study, we evaluated the tepotinib's potential to perpetrate pharmacokinetic drug interactions and modulate multidrug resistance (MDR). Accumulation studies showed that tepotinib potently inhibits ABCB1 and ABCG2 efflux transporters, which was confirmed by molecular docking. In addition, tepotinib inhibited several recombinant cytochrome P450 (CYP) isoforms with varying potency. In subsequent drug combination experiments, tepotinib synergistically reversed daunorubicin and mitoxantrone resistance in cells with ABCB1 and ABCG2 overexpression, respectively. Remarkably, MDR-modulatory properties were confirmed in ex vivo explants derived from NSCLC patients. Furthermore, we demonstrated that anticancer effect of tepotinib is not influenced by the presence of ABC transporters associated with MDR, although monolayer transport assays designated it as ABCB1 substrate. Finally, tested drug was observed to have negligible effect on the expression of clinically relevant drug efflux transporters and CYP enzymes. In conclusion, our findings provide complex overview on the tepotinib's drug interaction profile and suggest a promising novel therapeutic strategy for future clinical investigations.

Transmission electron microscopes use electrons with wavelengths of a few picometers, potentially capable of imaging individual atoms in solids at a resolution ultimately set by the intrinsic size of an atom. However, owing to lens aberrations and multiple scattering of electrons in the sample, the image resolution is reduced by a factor of 3 to 10. By inversely solving the multiple scattering problem and overcoming the electron-probe aberrations using electron ptychography, we demonstrate an instrumental blurring of less than 20 picometers and a linear phase response in thick samples. The measured widths of atomic columns are limited by thermal fluctuations of the atoms. Our method is also capable of locating embedded atomic dopant atoms in all three dimensions with subnanometer precision from only a single projection measurement., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Pulmonary arteriovenous malformation (PAVM) is formed by abnormal connections between pulmonary arteries and veins that bypass the pulmonary capillaries and transport deoxygenated blood through pulmonary veins to the left heart. This causes insufficient oxygenation of blood in the lungs. This condition remains symptomless for a long period of time. The most common symptoms include shortness of breath on exertion, nosebleeds, increased fatigue and a gradual development of cyanosis. Paradoxical embolism in the brain is a serious complication; it can present with a stroke or a brain abscess. Treatment of the disease consists of embolization of the pathological vascular connections, surgical resection of the affected pulmonary parenchyma and management of concomitant manifestations of the disease. PAVM in most common cases arises as a result of an autosomal dominant hereditary disorder referred to as hereditary hemorrhagic telangiectasia.  Case report: In our communication, we document the diagnostic and therapeutic management in a young patient diagnosed with PAVM after falling off his bicycle. Based on comprehensive assessments, AV malformations with a 40% shunt of the pulmonary circulation were detected. An angiographic procedure was not an appropriate option considering the type and extent of the condition. Therefore, video-assisted thoracic resection of the affected pulmonary lobe was indicated. Conclusion: PAVM is a rare finding. PAVM should be ruled out in all patients with hereditary hemorrhagic telangiectasia (HHT) signs in the oral cavity. Contrast sonography of the heart and contract CT of the chest are the methods of choice for the diagnosis. Conservative or pharmacological treat-ment fails to improve the patients status.  The condition is usually managed by embolization. Cases where PAVM is rather extensive or diffuse, where endovascular management would be inappropriate, can be well managed using endoscopic resection adequate to the extent of the condition.

We study the interplay between epitaxial strain, film thickness, and electric field in the creation, modification, and design of distinct ferroelastic structures in PbTiO 3 thin films. Strain and thickness greatly affect the structures formed, providing a two-variable parameterization of the resulting self-assembly. Under applied electric fields, these strain-engineered ferroelastic structures are highly malleable, especially when a / c and a 1 / a 2 superdomains coexist. To reconfigure the ferroelastic structures and achieve self-assembled nanoscale-ordered morphologies, pure ferroelectric switching of individual c -domains within the a / c superdomains is essential. The stability, however, of the electrically written ferroelastic structures is in most cases ephemeral; the speed of the relaxation process depends sensitively on strain and thickness. Only under low tensile strain-as is the case for PbTiO 3 on GdScO 3 -and below a critical thickness do the electrically created a / c superdomain structures become stable for days or longer, making them relevant for reconfigurable nanoscale electronics or nonvolatile electromechanical applications.

Achieving efficient spatial modulation of phonon transmission is an essential step on the path to phononic circuits using "phonon currents". With their intrinsic and reconfigurable interfaces, domain walls (DWs), ferroelectrics are alluring candidates to be harnessed as dynamic heat modulators. This paper reports the thermal conductivity of single-crystal PbTiO 3 thin films over a wide variety of epitaxial-strain-engineered ferroelectric domain configurations. The phonon transport is proved to be strongly affected by the density and type of DWs, achieving a 61% reduction of the room-temperature thermal conductivity compared to the single-domain scenario. The thermal resistance across the ferroelectric DWs is obtained, revealing a very high value (≈5.0 × 10 -9 K m 2 W -1 ), comparable to grain boundaries in oxides, explaining the strong modulation of the thermal conductivity in PbTiO 3 . This low thermal conductance of the DWs is ascribed to the structural mismatch and polarization gradient found between the different types of domains in the PbTiO 3 films, resulting in a structural inhomogeneity that extends several unit cells around the DWs. These findings demonstrate the potential of ferroelectric DWs as efficient regulators of heat flow in one single material, overcoming the complexity of multilayers systems and the uncontrolled distribution of grain boundaries, paving the way for applications in phononics.

Introduction: Injury to the heart during chest drainage is a very rare but potentially fatal complication of the procedure., Case Report: A 56-year-old, polymorbid, poorly co-operative and extremely obese patient with chronic cardiac subcompensation and pleural effusion was admitted to a district hospital. A drain was inserted into the left pleural cavity in order to evacuate the pleural effusion. Fresh oxygenated blood was flowing out from the drain. The drain was clamped immediately. Echocardiography showed drain insertion into the left ventricle. A cardiac surgeon was contacted and indicated patient transfer to a cardiac surgery department followed by an emergency surgery. During the surgery performed through a left thoracotomy, a defect in the left ventricular wall was sutured. The patient was then stabilized, transferred back to the district hospital and, after achieving cardiopulmonary compensation, discharged home., Conclusion: Injury to the heart in chest drainage is a very serious iatrogenic complication. If it is to be managed successfully, the site of the insertion of the drain tip needs to be correctly identified and the drain must not be extracted. A surgical department capable of adequately addressing this complication needs to be contacted promptly, as emergency surgery may be the only lifesaving possibility.Key words: chest drainage - complication - heart injury.

Pesticide transport from seed dressings toward subsurface tile drains is still poorly understood. We monitored the neonicotinoid insecticides imidacloprid and thiamethoxam from sugar beet seed dressings in flow-proportional drainage water samples, together with spray applications of bromide and the herbicide S-metolachlor in spring and the fungicides epoxiconazole and kresoxim-methyl in summer. Event-driven, high first concentration maxima up to 2830 and 1290 ng/L for thiamethoxam and imidacloprid, respectively, were followed by an extended period of tailing and suggested preferential flow. Nevertheless, mass recoveries declined in agreement with the degradation and sorption properties collated in the groundwater ubiquity score, following the order bromide (4.9%), thiamethoxam (1.2%), imidacloprid (0.48%), kresoxim-methyl acid (0.17%), S-metolachlor (0.032%), epoxiconazole (0.013%), and kresoxim-methyl (0.003%), and indicated increased leaching from seed dressings compared to spray applications. Measured concentrations and mass recoveries indicate that subsurface tile drains contribute to surface water contamination with neonicotinoids from seed dressings.

Castlemans disease is the term for reactive lymphocytary and plasmocytary proliferation which occurs in the unicentric (localized) form, usually without systemic symptoms, or in the generalized/multicentric form, typically with systemic symptoms (www.vzacne-diagnozy.cz). Over the past 25 years we diagnosed, treated and followed 14 histologically proven cases of Castlemans diseases. Seven patients had the localised form of the disease. In 5 of 7 cases the pathological lesion was located intrathoracically or intraabdominally and in only 2 cases it was on the surface of the body. No clinical symptoms were present in any of the patients with the unicentric form of the disease and surgical treatment led to the total removing of the disease in all of them. As opposed to that, all 7 patients with the multicentric form of Castlemans disease experienced febrile or subfebrile temperatures. Three of the 7 patients complained of severe troubling night sweats. Clinical expressions of vasculitis which was the cause of stroke, were present in 1 of 7 patients. Osteosclerotic changes on the skeleton were detected in 1 patient, who also suffered from fluid retention likely associated with this disease. Polyclonal propagation of immunoglobulins, predominantly immunoglobulin IgG type, was present in 5 of 7 patients with the multicentric form. In one case there was one complete molecule of monoclonal imunoglobuline present and in one case loose light chains κ were increased More than 1 sampling of material for histological examination of enlarged lymph nodes were needed in 6 of 7 patients for diagnosing the multicentric form of the disease. It has turned out beneficial with respect to diagnosing the disease to carry out surgical removal and histological examination of the nodes which accumulated the most fluorodeoxyglucose within PET-CT examination. The text describes experience of the treatment. In recent years the basis for the treatment has been the monoclonal antibody antiCD20 rituximab, or thalidomide and lenalidomide, or possibly their combination. The new medicine for these patients is interleukin-6 antibody called siltuximab (Sylvant), of which we have no own experience so far. Five of our seven patients with the multicentric form received treatment, 1 patient refused treatment and in one patient the signs of the disease activity are not expressed to such extent that would require treatment. The therapy containing rituximab reached complete remission in 2 patients and the therapy containing thalidomide and lenalidomide achieved the complete remission of the disease in 3 patients. In one of the above described cases the disease did not respond to the initial treatment with rituximab and remission was reached by thalidomide and lenalidomide and in one case the disease did not respond to the initial treatment with thalidomide and complete remission was reached with rituximab. Following the treatment, no patient with the multicentric form of Castlemans disease has had a relapse until now.

The authors describe their experience with surgical treatment of benign rare lymph proliferation - Castlemans disease (CD). It occurs in unicentric and multicentric forms. The very low incidence of the disease makes it very difficult to design larger prospective studies. Cases of two leading localizations of the unicentric form of CD - intrathoracic and retroperitoneal with special emphasis on the preoperative diagnosis and imaging options are described. This article underlines the curative potential of surgical treatment where a complete resection of the affected lymph node leads to eradication in almost 100% of the cases. The discussion is focused on the forms of CD - different localization, clinical symptoms and course of disease. It discusses the differential diagnosis, particularly difficult in the multicentric form, emphasizing the need to exclude malignant lymphoma. The etiopathogenesis of the disease is presented, mentioning its association with HIV (Human Immunodeficiency Virus) infection and HHV-8 (Human herpers virus 8) infection and the importance of overproduction of proinflammatory cytokines. The importance of surgical therapy for the unicentric form of CD is highlighted as compared to the multicentric form, where the surgeon´s task involves taking a biopsy - required for an accurate diagnosis.Key words: Castlemans disease - lymphoproliferation - lymphadenopathy - surgical treatment.