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DNA repair proteins became the popular targets in research on cancer treatment. In our studies we hypothesized that inhibition of DNA polymerase theta (Polθ) and its combination with Poly (ADP-ribose) polymerase 1 (PARP1) or RAD52 inhibition and the alkylating drug temozolomide (TMZ) has an anticancer effect on glioblastoma cells (GBM21), whereas it has a low impact on normal human astrocytes (NHA). The effect of the compounds was assessed by analysis of cell viability, apoptosis, proliferation, DNA damage and cell cycle distribution, as well as gene expression. The main results show that Polθ inhibition causes a significant decrease in glioblastoma cell viability. It induces apoptosis, which is accompanied by a reduction in cell proliferation and DNA damage. Moreover, the effect was stronger when dual inhibition of Polθ with PARP1 or RAD52 was applied, and it is further enhanced by addition of TMZ. The impact on normal cells is much lower, especially when considering cell viability and DNA damage. In conclusion, we would like to highlight that Polθ inhibition used in combination with PARP1 or RAD52 inhibition has great potential to kill glioblastoma cells, and shows a synthetic lethal effect, while sparing normal astrocytes.

This study aimed to summarize our experience with modified drilling epiphysiodesis and prediction methods for accurate timing of surgery and to compare the results with those of recent work by other authors. The Macnicol and Gupta modified drilling technique was used. Distal femoral and/or proximal tibial permanent epiphysiodesis was performed in 42 children (21 boys, 21 girls; median age at surgery=12.6 years, age range=9.4-15.4 years) between 2004 and 2016. Based on the groundwork of previous studies, we developed an auxological prediction method. The limb length discrepancy (LLD) was assessed by clinical examination and verified by an x-ray of the hips when standing with blocks under the shorter leg. The predicted shortening was 2.7 cm ± 1.1 cm. The final discrepancy after finishing skeletal growth was 0.5 ± 0.5 cm. In 26 patients (61.9%), equalization of both legs was achieved (0-0.5 cm). In 4 patients (9.5%), the remaining shortening was more than 1.0 cm. Shortening of an initially longer leg occurred in two patients (0.5 cm and 0.6 cm). Failure of growth plate arrest was observed in 1 patient. In another 3 patients, the efficacy of tibial epiphysiodesis was unsatisfactory. Minor complications occurred in 5 cases, but there was no evidence of angular deformity in the frontal and sagittal planes or proximal fibula overgrowth. Three patients (7.1%) returned to the operating room. Compared to published data, more patients achieved complete equalization of leg length. The results of this study verified the accuracy of the auxological prediction algorithm of LLD based on Shapiro's findings. The surgical outcome is comparable between Shapiro patterns 1 and 3. Auxological examination, assessment of bone age, and sexual maturation are crucial tools for accurate timing of surgery.

HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme. At the molecular level, VPA leads to a downregulation of FANCD2 and RAD51, and the eradication of glioblastoma cells. The results of this study indicate that combining HDACi with PARPi could potentially enhance the treatment of glioblastoma, the most aggressive type of cancer that originates in the brain.

The superior cerebellar artery (SCA) arises from the distal part of the basilar artery and passes by the oculomotor, trochlear, and trigeminal nerves. SCA is known to play a crucial role in the development of trigeminal neuralgia. However, due to its anatomical variability, it may also trigger other neurovascular compression (NVC), including hemifacial spasm, oculomotor nerve palsy, and ocular neuromyotonia. Additionally, it may be associated with ischemic syndromes and aneurysm development, highlighting its clinical significance. The most common anatomical variations of the SCA include duplication, a single vessel origin from the posterior cerebral artery (PCA), and a common trunk with PCA. Rarely observed variants include bifurcation and origin from the internal carotid artery. Certain anatomical variants such as early bifurcation and caudal course of duplicated SCA trunk may increase the risk of NVC. In this narrative review, we aimed to examine the impact of the anatomical variations of SCA on the NVCs based on papers published in Pubmed, Scopus, and Web of Science databases with a snowballing approach. Our review emphasizes the importance of a thorough understanding of the anatomical variability of SCA to optimize the management of patients with NVCs associated with this artery.

The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor-valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673-PARP1 inhibitor-PARPi) and/or Dacarbazine (DTIC-alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells. Furthermore, the pharmacological inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-673. In addition, the inhibition of HDACs causes the sensitization of melanoma cells to DTIV and BMN-673 in melanoma xenografts in vivo. At the mRNA and protein level, the histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study aims to demonstrate that combining an HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is commonly recognized as being among the most aggressive malignant tumors. The findings presented here point to a scenario in which HDACs, via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Background: Tumors of the fourth ventricle are exceedingly rare; however, such lesions are formidable due to the severe postoperative neurological complications (pNCs) which often occur. The adoption of the telovelar approach over the transvermian was created to supposedly mitigate the pNCs; however, there is a lack of sufficient data supporting this theory., Methods: Records from six hospitals were reviewed for patients surgically treated for a single tumor within the 4 th ventricle from 2016 to 2022. The pNCs which had 10 or more occurrences among the patients were individually assessed as the dependent variable in a binary logistic regression model against covariates which included the surgical approach., Results: This study of 67 patients confirms no significant differences in risk for pNCs between the transvermian and telovelar approach. Rather, multivariate analysis identified neurophysiological monitoring (IONM) as a protective factor for postoperative speech and swallowing defects (odds ratio [OR]: 0.076, 95% confidence interval [CI] 0.011-0.525). Furthermore, intraoperative external ventricular drainage (EVD) was a protective factor for postoperative gait and focal motor defects (OR: 0.075, 95% CI 0.009-0.648) and for postoperative hydrocephalus (OR: 0.020, 95% CI 0.002-0.233). A univariate meta-analysis pooling the present study's patients and an additional 304 patients from the three additional studies in the literature confirms no significant differences in risk between the transvermian and telovelar approach for pNCs., Conclusion: Intraoperative adjuncts including IONM and EVD may play a significant role in the postoperative outcome. Despite the present study's sample size being a major limitation, the findings may provide great value to neurosurgeons given the scarcity of the current literature., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)

Although the microanatomy of Meckel's cave (MC) has been well studied, there are still controversies regarding the meningeal architecture of the space. Moreover, there are only general mentions of the arachnoid granulations near MC in just a few sources. This study is aimed at determining the frequency, location, and anatomical variability of the main clusters of arachnoid granulations around MC. The dissection involved 26 isolated specimens of MC fixed in formalin (neutral buffered, 10%). This number included five freshly harvested specimens examined histologically. Additional paraffin block with MC horizontal section was taken from our neuroanatomical collection. Carefully selected anatomical and histological techniques were applied to assess the complex relationships between the arachnoid granulations and adjacent structures. Arachnoid granulations were found around MC in all specimens with different anatomical variations. The main clusters of arachnoid granulations were close to the trigeminal ganglion and its divisions. The dorsolateral wall of MC was a thick layer formed by interweaving bundles of collagen fibers arranged in various directions. The entire MC was surrounded by a dural sleeve (envelope). This sleeve separated MC from the lateral sellar compartment. At its anterior (rostral) end, it formed a cribriform area pierced by individual fascicles of the trigeminal nerve's primary divisions. The connective tissue forming the sleeve was not only continuous with the epineurium but also shifted to the perineuria surrounding individual nerve fascicles. The meningeal architecture around MC has a complex and multilayer arrangement with a collagenous sleeve closely related to the trigeminal ganglion. Arachnoid granulations are typically found around MC., (© 2023. The Author(s).)

The objective of this meta-analysis was to present transparent data on the morphology of the pituitary gland (PG) using the available data in the literature. The main online medical databases, such as PubMed, Embase, Scopus, and Web of Science, were searched to gather all relevant studies regarding PG morphology. The mean overall volume of the PG was found to be 597.23 mm 3 (SE = 28.81). The mean overall height of the PG was established to be 5.64 mm (SE = 0.11). The mean overall length of the PG was found to be 9.98 mm (SE = 0.26). In the present study, the PG's overall morphology and morphometric features were analyzed. Our results showed that, on average, females from Asia have the highest volume of PG (706.69 mm 3 ), and males from Europe have the lowest (456.42 mm 3 ). These values are crucial to be aware of because they represent the normal average properties of the PG, which may be used as reference points when trying to diagnose potential pathologies of this gland. Furthermore, the present study's results prove how the PG's size decreases with age. The results of the present study may be helpful for physicians, especially surgeons, performing procedures on the PG.

Introduction: In this paper, we have analysed all hand glomangioma cases referred to our clinic in the context of symptoms, time to diagnosis, and the role of surgical resection of the lesion., Material and Methods: We have collected the following data: the presence of risk factors, manifestation, time to diagnosis, the treatment applied, and follow-up of patients., Results: We have collected medical records from six patients, three males and three females. The median age was 45 (IQR: 29.5-65.75). The main symptom in all patients was severe pain and tenderness. The first-choice physician(s) were: general practitioners, general surgeons, and neurologists. The median time to diagnosis was 7 (IQR: 5-10) years. The main complaint of our patients was severe pain - 9 (IQR: 9-10) on the VAS scale, which was significantly alleviated after surgical treatment - 0 (IQR: 0-0; p = 0.043)., Conclusions: Extremely long times to final diagnosis, and excellent outcomes of surgical treatment, highlight the necessity of raising awareness of glomangiomas among clinicians.

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26 , ITGA2B , and F8 ) and helped us to identify suspected variants ( NBEAL2 , F2 , BLOC1S6 , AP3D1 , GP1BB , ANO6 , CD36 , and ITGB3) and new suspected variants ( GFI1B , FGA , GP1BA , and ITGA2B ) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.

Intramedullary spinal cord abscess (ISCA) is a rare clinical pathology of the central nervous system that usually accompanies other underlying comorbidities. Traditionally it has been associated with significant mortality and neurological morbidities because it is often difficult to diagnose promptly, owing to its nonspecific clinical and neuroimaging features. The mortality rate and the outcome of these infections have been improved by the introduction into clinical practice of antibiotics, advanced neuroimaging modalities, and immediate surgery. We report the case of a 65-year-old male patient who presented with a progressive spastic gait and lumbar pain, predominantly in the left leg. An MRI image revealed an expansile intramedullary cystic mass in the thoracic spinal cord, which was initially diagnosed as a spinal tumor. He underwent laminectomy and myelotomy, and eventually the pus was drained from the abscess. The follow-up MRI showed improvement, but the patient's paraplegia persisted. In light of his persistent hypoesthesia and paraplegic gait with developing neuropathic pain, he was readmitted, and an MRI of his lumbar spine revealed multilevel degenerative disease and tethered spinal cord syndrome with compression of the medulla at the L2-L3 level. The patient underwent central flavectomy with bilateral foraminotomy at the L2-L3 level, and the medulla was decompressed. Postoperatively, his neurological symptoms were significantly improved, and he was discharged from hospital on the third day after admission. In support of our case, we systematically reviewed the recent literature and analyzed cases published between 1949 and May 2022, including clinical features, mechanisms of infection, predisposing factors, radiological investigations, microbial etiologies, therapies and their duration, follow-ups, and outcomes. Initial clinical presentation can be misleading, and the diagnosis can be challenging, because this condition is rare and coexists with other spinal diseases. Hence, a high index of suspicion for making an accurate diagnosis and timely intervention is required to preclude mortality and unfavorable outcomes. Our case is a clear example thereof. Long-term follow-up is also essential to monitor for abscess recurrences.

Intramedullary spinal cord abscesses (ISCA) are rare. Typical symptoms include signs of infection and neurological deficits. Symptoms among (younger) children can be highly uncharacteristic. Therefore, prompt and proper diagnoses may be difficult. Typical therapeutic options include antibiotics and neurosurgical exploration and drainage. In this review, we analyze published cases of ISCA among children. Most pediatric cases were found to be under the age of 6 years. The typical symptoms included motor deficits in 89.06%, infection signs in 85.94%, and sensory deficits in 39.06%. Urinary dysfunction was observed in 43.75%, and bowel dysfunction in 17.19%. The predisposing factors included dermal sinuses, (epi)dermoid cysts, prior infection, iatrogenic disorder, and trauma. The most common pathogens were: Staphylococcus aureus , Mycobacterium tuberculosis , Escherichia coli , and Proteus mirabilis . The pediatric population has good outcomes as 45.93% of patients had complete neurological recovery and only 26.56% had residual neurological deficits. Fifteen (23.44%) had persistent neurological deficits. Only one (1.56%) patient died with an ISCA. In two (3.13%) cases, there were no details about follow-up examinations.

Thoracic osteophytes are a common feature of degenerative spine disease. However, it is rare that osteophytes overgrowth on the anterior surface of thoracic spine results in the compression of vital structures and causes symptoms. A 39-year old man with a two-year history of thoracic and upper abdominal pain was admitted to the neurosurgery ward after having been seen by several specialists. Thoracic spine MRI and CT scans were analyzed. Osteophytes were identified on the anterolateral right side at level T8-T9 and were indicated as a possible cause of the symptoms. After obtaining patient consent, surgery was performed with transthoracic access to the anterolateral surface of the spine. Intraoperatively, the greater splanchnic nerve was released by osteophyte removal. The patient reported improvement of the preoperative symptoms at the six-month and two-year follow-up visit. Postoperative MRI indicated complete osteophyte excision. To the best of our knowledge, this is the first report of symptomatic sympathetic trunk branch compression by thoracic osteophytes., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: This report presents a series of cases representing variant origin and course of the ulnar artery, namely the superficial ulnar artery (SUA), observed during the review of collection of historical specimens prepared in the 19th century by the prominent Polish anatomist Ludwik Karol Teichmann and his collaborators, exhibited in the Anatomy Museum of Jagiellonian University Medical College., Results: Three distinct variants of the SUA were found on anatomical specimens of the upper limb with arteries injected by using Teichmann's method. In case no. 1, the SUA originated from the brachial artery slightly above the interepicondylar line of the humerus. This aberrant vessel gave off the common interosseous artery in the upper half of the cubital fossa and then ran superficially to the bicipital aponeurosis and over the muscles arising from the medial epicondyle of the humerus. The cases no. 2 and 3 involved two similar variants of the superficial artery in which the common interosseous artery arose from the radial artery. In the unique case no. 4, the SUA arose from the radial artery., Conclusions: The SUA shows diverse anatomy regarding its topography and blood supply territory. Orthopaedic, hand, and plastic surgeons should be aware of anatomic variations of the SUA both in planning and in conducting surgeries of the upper limb.

Spectroscopic methods provide information on the spatial localization of biochemical components based on the analysis of vibrational spectra. Raman spectroscopy and Raman imaging can be used to analyze various types of human brain tumors and breast cancers. The objective of this study is to evaluate the Raman biomarkers to distinguish tumor types by Raman spectroscopy and Raman imaging. We have demonstrated that bands characteristic for carotenoids (1156 cm -1 , 1520 cm -1 ), proteins (1004 cm -1 ), fatty acids (1444 cm -1 , 1655 cm -1 ) and cytochrome (1585 cm -1 ) can be used as universal biomarkers to assess aggressiveness of human brain tumors. The sensitivity and specificity obtained from PLS-DA have been over 73%. Only for gliosarcoma WHO IV the specificity is lower and takes equal 50%. The presented results confirm clinical potential of Raman spectroscopy in oncological diagnostics., 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 © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The present study examines the use of receptive emotional and linguistic prosody in patients with schizophrenia; particularly, its aim was to evaluate the type and number of errors made when comprehending the emotions and modes implied by meaningless utterances. Seventy-eight participants were enrolled to the study, i.e. two groups (patients with schizophrenia and healthy controls) consisting of 39 subjects. The severity of illness was evaluated with the Positive and Negative Syndrome Scale; comprehension of emotional and linguistic prosody was assessed by the subtests of the Polish Version of the Right Hemisphere Language Battery. Neither emotional nor linguistic prosody comprehension both correlated with schizophrenia symptoms. The study group experienced more difficulties in distinguishing between happiness and anger, and were more likely to misunderstand imperative utterances, confusing them with interrogative or affirmative ones. Such impairments are significant as they may affect the ability to form and sustain relationships with other people, achieve success in the work environment, and integrate in the community. They may also be a trait mark of the illness independent of psychotic symptoms. Further research is needed to translate this knowledge into meaningful and therapeutic interventions to improve quality of life, both for affected individuals and for their communication partners., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Anterior cervical discectomy and fusion (ACDF) is an effective method in treating cervical sagittal imbalance and spine deformations., Objectives: The aim of this work was to assess whether changes of the Cobb angle, sagittal vertical axis (SVA) and T1 slope parameters affect the outcomes of surgical treatment., Material and Methods: A prospective study was performed in 30 patients qualified for surgical treatment for cervical degenerative disc disease. The ACDF was performed on 2 levels. Every patient underwent an X-ray examination before surgery and 3 months after the procedure. The following parameters were assessed: the T1 slope, the angle of cervical lordosis, the SVA distance, quality of life assessed using the Neck Disability Index (NDI), and perceived pain measurement assessed using the Visual Analogue Scale (VAS)., Results: The cervical lordosis angle significantly changed (p < 0.01) to an average of 11.52°. The SVA C2-C7 distance significantly decreased (p < 0.001) to an average of 21.06 mm. The value of the T1 slope angle did not change significantly before and after surgery (p = 0.706). After surgery, statistically significant improvement was achieved on the NDI scale for neck pain (p < 0.001) to an average of 9. The NDI score significantly decreased over time (p < 0.001), and this change was significantly related to the increased Cobb angle (p = 0.036)., Conclusions: Improvement in cervical lordosis C2-C7 can improve the outcomes of surgical treatment. Preoperative analysis of X-rays and sagittal balance parameters may be beneficial for treatment outcomes.

Malignant peripheral nerve sheath tumors (MPNST) are rare but one of the most aggressive types of cancer. Currently, there are no effective chemotherapy strategies for these malignancies. The inactivation of the neurofibromatosis type I (NF1) gene, followed by loss of TP53, is an early stage in MPNST carcinogenesis. NF1 is a negative regulator of the Ras proteins family, which are key factors in regulating cell growth, homeostasis and survival. Cell cycle dysregulation induces a stress phenotype, such as proteotoxic stress, metabolic stress, and oxidative stress, which should result in cell death. However, in the case of neoplastic cells, we observe not only the avoidance of apoptosis, but also the impact of stress factors on the treatment effectiveness. This review focuses on the pathomechanisms underlying MPNST cells physiology, and discusses the possible ways to develop a successful treatment based on the molecular background of the disease.

The anterior cingulate cortex is considered to play a crucial role in cognitive and affective regulation. However, this area shows a high degree of morphological interindividual variability and asymmetry. It is especially true regarding the paracingulate sulcus and paracingulate gyrus (PCG). Since the reports described in the literature are mainly based on imaging techniques, the goal of this study was to verify the classification of the PCG based on anatomical material. Special attention was given to ambiguous cases. The PCG was absent in 26.4% of specimens. The gyrus was classified as present in 28.3% of cases. The prominent type of the PCG was observed in 37.7% of the total. Occasionally, the gyrus was well-developed and roughly only a few millimeters were missing for classifying the gyrus as prominent, as it ended slightly anterior the level of the VAC. The remaining four cases involved two inconclusive types. We observed that the callosomarginal artery ran within the cingulate sulcus and provided branches that crossed the PCG. Based on Klingler's dissection technique, we observed a close relationship of the PCG with the superior longitudinal fascicle. The awareness of the anatomical variability observed within the brain cortex is an essential starting point for in-depth research.

The present study aims to provide detailed observations on the cavernous segment of the abducens nerve (AN), emphasizing anatomical variations and the relationships between the nerve and the internal carotid plexus. A total of 60 sides underwent gross-anatomical study. Five specimens of the AN were stained using Sihler's method. An additional five specimens were subjected to histological examination. Four types of AN course were observed: a single nerve along its entire course, duplication of the nerve, division into separate rootlets at the point of contact with the cavernous part of the internal carotid artery (ICA), and early-branching before entering the orbit. Due to the relationships between the ICA and internal carotid plexus, the cavernous segment of the AN can be subdivided into a carotid portion located at the point of contact with the posterior vertical segment of the cavernous ICA and a prefissural portion. The carotid portion of the cavernous AN segment is a place of angulation, where the nerve always directly adheres to the ICA. The prefissural portion of the AN, in turn, is the primary site of fiber exchange between the internal carotid plexus and either the AN or the lateral wall of the cavernous sinus.

The inferomedial triangle is one of the two surgical triangles in the paraclival subregion of the skull base. It is delineated by the posterior clinoid process, the dural entrance of the trochlear nerve and the dural entrance of the abducens nerve. The aim of the present article is to describe the anatomical variations within the inferomedial triangle. Measurements of the triangle's borders and area were supplemented by detailed observations of the topographical anatomy and various arrangements of its contents. Nine adult cadaveric heads (18 sides) and 28 sagittal head sections were studied. The mean area of the inferomedial triangle was estimated to be 60.7 mm 2 . The mean lengths of its medial, lateral and superior borders were 16.1 mm, 11.9 mm and 10.4 mm, respectively. The dorsal meningeal artery was identified within the inferomedial triangle in 37 out of 46 sides (80.4%). A well-developed petrosphenoidal ligament of Grüber was identified within the triangle on 36 sides (78.3%). Although some structures were variable, the constant contents of the inferomedial triangle were the posterior petroclinoid dural fold, the upper end of the petroclival suture, the gulfar segment of the abducens nerve and the posterior genu of the intracavernous internal carotid artery.

Background: We investigated several aspects that could affect the role of the European earwig (Forficula auricularia) as a generalist predator in orchards: (i) seasonal activity in apple orchards, (ii) effectiveness of two cardboard trap types (roll vs tape) to enhance earwig densities, (iii) the effect of pesticides (chlorpyrifos-methyl, spinosad, indoxacarb, spirotetramat, pirimicarb, sulphur, fluopyram tebuconazole) on earwig survival and behaviour, and (iv) the perception of European fruit growers of the earwigs' role as a predator or pest., Results: The highest activity of earwigs in apple trees was observed in summer. Roll traps were a more effective capture method than tape traps. The roll traps also significantly increased earwig abundances in trees. Only the earwigs exposed to the insecticides indoxacarb, spinosad and chlorpyrifos-methyl had significantly higher mortality and more erratic behaviour than earwigs from the control treatment. Earwigs from orchards with long-term (>10 years) application of chlorpyrifos-methyl had significantly lower mortality when exposed to this insecticide than earwigs from nonsprayed orchards. The fruit growers perceived earwigs as natural enemies of aphids and psyllids but also as pests. However, they regarded the damage caused by earwigs as economically unimportant without the necessity for management against them., Conclusion: Fruit growers can increase earwig densities by installing rolled cardboard bands around trees. The highest seasonal activity of European earwigs coincides with applications of insecticides in orchards. This could disturb the earwigs' potential to suppress pest populations because several insecticides widely used in orchards have lethal and sublethal effects on earwigs even though they seem to develop some degree of pesticide resistance over time. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.

We developed a practical and cost-effective method of production of a 3D-printed model of the arterial Circle of Willis of patients treated because of an intracranial aneurysm. We present and explain the steps necessary to produce a 3D model from medical image data, and express the significant value such models have in patient-specific pre-operative planning as well as education. A Digital Imaging and Communications in Medicine (DICOM) viewer is used to create 3D visualization from a patient's Computed Tomography Angiography (CTA) images. After generating the reconstruction, we manually remove the anatomical components that we wish to exclude from the print by utilizing tools provided with the imaging software. We then export this 3D reconstructions file into a Standard Triangulation Language (STL) file which is then run through a "Slicer" software to generate a G-code file for the printer. After the print is complete, the supports created during the printing process are removed manually. The 3D-printed models we created were of good accuracy and scale. The median production time used for the models described in this manuscript was 4.4 h (range: 3.9-4.5 h). Models were evaluated by neurosurgical teams at local hospital for quality and practicality for use in urgent and non-urgent care. We hope we have provided readers adequate insight into the equipment and software they would require to quickly produce their own accurate and cost-effective 3D models from CT angiography images. It has become quite clear to us that the cost-benefit ratio in the production of such a simplified model is worthwhile.

Healthcare workers are particularly exposed to biological risk during their daily occupational activities. Nowadays, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become one of the most widespread infectious agents. In the current study, we performed a survey on the attitude and behavior of Polish healthcare workers (HCW), which comprise physicians (MD) and administrative healthcare assistants (HA) towards the Coronavirus Disease 2019 (COVID-19) vaccination. Our study involved 2300 subjects (42.17% female; 10.96% MD; 5.87% HA). The evaluation was conducted using a Google Forms survey based on original questions and the Depression, Anxiety and Stress Scale-21 Items questionnaire. HCW significantly more often demonstrated their willingness to get vaccinated against the SARS-CoV-2 as compared to the control group (82.95% vs. 54.31%, respectively). The main concern, as regards all groups, was the development of long-term side effects after getting COVID-19 vaccine. The study revealed that depression significantly affects the willingness to get vaccinated. The readiness was significantly strengthened by positive medical history of recommended vaccinations, fear of catching COVID-19, as well as fear of passing on the disease to the relatives. Overall, the percentage of HCW, who want to be vaccinated against COVID-19 remains unsatisfactory. Further works exploring this subject are needed to take a step closer to achieving the herd immunity in the era of the COVID-19 pandemic.

To monitor redox state changes and biological mechanisms occurring in mitochondrial cytochromes in cancers improving methods are required. We used Raman spectroscopy and Raman imaging to monitor changes in the redox state of the mitochondrial cytochromes in ex vivo human brain and breast tissues at 532 nm, 633 nm, 785 nm. We identified the oncogenic processes that characterize human infiltrating ductal carcinoma (IDC) and human brain tumors: gliomas; astrocytoma and medulloblastoma based on the quantification of cytochrome redox status by exploiting the resonance-enhancement effect of Raman scattering. We visualized localization of cytochromes by Raman imaging in the breast and brain tissues and analyzed cytochrome c vibrations at 750, 1126, 1337 and 1584 cm -1 as a function of malignancy grade. We found that the concentration of reduced cytochrome c becomes abnormally high in human brain tumors and breast cancers and correlates with the grade of cancer. We showed that Raman imaging provides additional insight into the biology of astrocytomas and breast ductal invasive cancer, which can be used for noninvasive grading, differential diagnosis.

Since physicians play a key role in vaccination, the initial training of medical students (MS) should aim to help shape their attitude in this regard. The beginning of vaccination programs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an excellent time to assess the attitudes held by both medical and non-medical students regarding vaccination. A 51- to 53-item questionnaire including the Depression, Anxiety and Stress Scale was administered to 1971 students (49.21% male; 34.86% MS); two career-related questions were also addressed to the MS. The majority of surveyed students indicated a desire to get vaccinated against SARS-CoV-2, with more medical than non-medical students planning to get vaccinated (91.99% vs. 59.42%). The most common concern about SARS-CoV-2 infection was the risk of passing on the disease to elderly relatives. While conspiracy theories regarding the COVID-19 vaccine are less popular among MS, both groups indicated concerns that vaccines may cause autism is equally common (~5%). Further studies exploring social attitudes towards the SARS-CoV-2 vaccine are a necessary first step to optimizing vaccination programs and achieving herd immunity.

This report presents a detailed anatomical investigation of an upper limb specimen showing an atypical formation of the musculocutaneous nerve (MCN) and median nerve (MN). The study was refined by intraneural dissection, which supplements earlier descriptions of similar anatomical variations and allows for revision of the accepted classification. The case described in this report was an incidental finding during routine dissection of a fixed isolated upper limb. Intraneural dissection revealed partial fusion between the MCN and aberrant bundles of the MN. Those aberrant bundles joined the main steam of the MN at the level at which the MCN branched off as an independent nerve. The procedure allowed the aberrant fibres of the MN to be differentiated from the MCN. The presence of separate bundles in a territory corresponding to the MCN was confirmed, although those bundles and the aberrant MN bundles were covered by a common epineurium. The aberrant MN bundles running within the MCN did not contribute to innervation of the forearm muscles. They rejoined the main nerve trunk in the arm. A comprehensive understanding of the diverse anatomical variations of the upper limb nerves could be crucial for the safety and success of surgical procedures, especially procedures for reconstructing the brachial plexus or its branches.

Cell surface expression of PD-1, PD-L1 and PD-L2 immune checkpoints on B and T cells obtained from patients with mantle cell lymphoma shows ambiguous results across many studies and creates obstacles for the implementation of immune checkpoint inhibitors into the therapy of mantle cell lymphoma. Using multiparameter flow cytometry we analysed surface expression of PD-1, PD-L1 and PD-L2 molecules on B and T cells of 31 newly diagnosed mantle cell lymphomas and compared it with the results of 26 newly diagnosed chronic lymphocytic leukaemias and 20 healthy volunteers. To gain insight into the age-dependent changes of surface expression of these immune checkpoints, flow cytometric subanalysis of 30 healthy volunteers of 25-93 years of age was conducted. Overall, we demonstrated weak surface expression of PD-1, PD-L1 and PD-L2 on B and T cells of mantle cell lymphoma patients (< 10 % when compared to healthy individuals). A significant age-dependent increase in the expression of PD-1 and its ligand PD-L2 was observed in healthy volunteers. Our results suggest that neither PD-1 nor its ligands represent relevant druggable targets for the therapy of mantle cell lymphoma. The observed age-dependent changes in healthy population could impact efficiency of immune checkpoint inhibitors and could be at least partly connected with increased incidence of cancer with age.

Properties of amorphous materials are connected to the local structure at the nanoscale, which is typically described in terms of short- and medium-range order (SRO, MRO). Variable resolution fluctuation electron microscopy (VR-FEM) is a sensitive method to characterize the underlying characteristic length scale of MRO of amorphous samples (Voyles, Gibson and Treacy, J. Electron Microsc. 49 (2000) 259). VR-FEM data was acquired using scanning transmission electron microscopy (STEM), collecting a large number of nano-beam diffraction patterns (NBDPs) with various probe sizes. Here we present an advanced method to accelerate the calculation of simulated FEM normalized variance profiles using a newly developed simulation and analysis approach with segmented ring detectors using the program STEMcl (Radek et al., Ultramicroscopy 188 (2018) 24). VR-FEM simulations are based on structures obtained from molecular dynamics (MD) simulations. A comparison between simulated and experimental VR-FEM profiles with respect to peak position, ratio and shape (and intensity) show good agreement. Moreover, a crystalline cluster of 1 nm in size was embedded into the MD box to test the validity of the paracrystalline approximation with the pair-persistence analysis suggested by Gibson et al. (Gibson, Treacy and Voyles, Ultramicroscopy 83 (2000) 169). The corresponding VR-FEM simulation and calculation of MROs yield close results to the size of the initially embedded crystalline cluster, which supports both the paracrystalline approach and the validity of the segmented detector simulation. Additionally, we conclude that continuous random network (CRN) amorphous silicon models contain a higher degree of MRO than experimentally expected., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Percutaneous vertebroplasty is commonly used to treat spinal fractures. The authors compare radiation exposure as potential risk for the surgical team during vertebroplasty guided by O-arm combined with neuronavigation versus vertebroplasty guided by C-arm fluoroscopy., Material and Methods: The clinical material consisted of a group of 29 patients (44 vertebrae) with fractures of the thoracolumbar spine treated with percutaneous vertebroplasty guided by O-arm with neuronavigation. In this new method, the operating room staff leaves the operating room for the duration of the 3D scan of the appropriate spine section using the O-arm. In the next stage, the needle of the vertebroplasty system is introduced using only neuronavigation without the need for a radiological view. Finally, the cement injection was made under O-arm fluoroscopic control. The comparison group consisted of a group of 35 patients (40 vertebrae) treated with the classical method using C-arm fluoroscopy. The two methods were compared in terms of the average dose of emitted ionizing radiation through the device (O-arm vs. C-arm) to which surgeons are exposed during percutaneous vertebroplasty., Results: As a result of vertebroplasty procedures guided by neuronavigation, a statistically significant difference between the values of mean dose of radiation emitted by O-arm and C-arm systems was noted. The O-arm emitted 912 cGy/cm 2 vs. 1722 cGy/cm 2 emitted by the C-arm during fluoroscopically assisted procedures and 601.28 cGy/cm 2 vs. 1506.86 cGy/cm 2 per vertebrae., Conclusions: During vertebroplasty with the O-arm combined with neuronavigation the radiation dose is significantly lower as compared with the C-arm used for fluoroscopic guidance, minimizing the potential risk of radiation exposure to surgeons., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Cancer cells often accumulate spontaneous and treatment-induced DNA damage i.e. potentially lethal DNA double strand breaks (DSBs). Targeting DSB repair mechanisms with specific inhibitors could potentially sensitize cancer cells to the toxic effect of DSBs. Current treatment for glioblastoma includes tumor resection followed by radiotherapy and/or temozolomide (TMZ) - an alkylating agent inducing DNA damage. We hypothesize that combination of PARP inhibitor (PARPi) with TMZ in glioblastoma cells displaying downregulation of DSB repair genes could trigger synthetic lethality. In our study, we observed that PARP inhibitor (BMN673) was able to specifically sensitize DNA ligase 4 (LIG4)-deprived glioblastoma cells to TMZ while normal astrocytes were not affected. LIG4 downregulation resulting in low effectiveness of DNA-PK-mediated non-homologous end-joining (D-NHEJ), which in combination with BMN673 and TMZ resulted in accumulation of lethal DSBs and specific eradication of glioblastoma cells. Restoration of the LIG4 expression caused loss of sensitivity to BMN673+TMZ. In conclusion, PARP inhibitor combined with DNA damage inducing agents can be utilized in patients with glioblastoma displaying defects in D-NHEJ., Competing Interests: CONFLICTS OF INTEREST There is no conflicts of interest.

OBJECTIVEThe objective of the present study was to determine experimentally the distribution of lesions caused in the cadaveric brachial plexus (BP) by excessive stretching. The authors attempted to delineate the correlation between the direction of stretching and sites of lesions.METHODSFifteen specimens (each comprised the spinal segment C4-T2 with 2 BPs) were harvested from adult cadavers. Each BP was stretched in a mechanical testing machine at a constant speed of 200 mm/min. Specimens were divided into 3 groups: in group A the BPs were stretched caudally at a 45° angle to the spinal midline; in group B they were stretched perpendicularly to the spinal midline; and in group C the stretching was caudally parallel to the midline. Lesions of each BP were identified and analyzed. A graph of load against dislocation was registered when stretching to delineate the maximal force (Fmax), defined as the maximum load at which BP failure occurs.RESULTSBased on macroscopic examination, 140 sites of mechanical damage were identified in 30 BPs. Preganglionic injuries (63.6% of lesions), defined as avulsions of the spinal ganglia with their rootlets, were found in 89 spinal nerves. In group B-in which specimens were stretched perpendicularly to the spinal segment-preganglionic injuries were significantly more frequent (41 avulsed spinal nerves) than in groups A and C (21 and 27 avulsed spinal nerves, respectively). Postganglionic lesions equivalent to neurotmesis were found in 51 sites (36.4% of all lesions) along spinal nerves, trunks, divisions, and cords. Postganglionic lesions in group B were much less frequent (8) as compared with groups A and C (24 and 19, respectively).CONCLUSIONSPredominance of preganglionic lesions suggests that attachments of the BP to the spine are more susceptible to traction than postganglionic elements. Preganglionic lesions were mainly produced in C7, C8, and T1 spinal nerves, suggesting their weaker attachment to the spine than in the case of C5 and C6 nerves. Preganglionic lesions were highly correlated with a traction perpendicular to the spine, whereas postganglionic lesions were provoked mainly by traction directed at 45° caudally or by means of caudal traction parallel to the midline. This discrepancy implies a relationship between mechanical resistance of pre- and postganglionic elements of the BP and the vector of force.

Objective: In postmenopausal period, changes in bone turnover markers (BTM), vitamin D3, cytokines and parathyroid hormone (PTH) are frequently observed. The study was to assess bone mineral density (BMD) and bone metabolism index (IBM) in the perimenopausal women., Design Years: 2013-2014., Subjects and Methods: One hundred and thirteen women were divided into four groups: group I (35 not menstruating 50 - 60 years old with osteoporosis), II (23 not menstruating 50 - 60 years old without osteoporosis), III (30 menstruating 40 - 49 years old with osteoporosis), IV (25 menstruating 40 - 49 years old without osteoporosis). The following parameters were measured: IL-1β, IL-6, TNF-α, hormone oestradiol (E2), PTH, FSH, TSH, calcium (Ca 2+ ), phosphates (P), alkaline phosphatase (bALP), C-terminal telopeptide of type I collagen alpha 1 chain (α1CTX), osteocalcin (OC), BMD, IBM., Results: IBM and BMD were significantly lower in premenopausal than in postmenopausal women. The concentration of OC, CTX, 25OH D3 and PTH levels differed significantly between group I vs . II, group I vs . III and group II vs . IV., Conclusions: The levels of BTM, D3, PTH differed significantly between groups. This study demonstrated that bone metabolism depended mainly on processes related with menopause state and changes in D3, PTH and cytokines levels., Competing Interests: The authors declare that they have no conflict of interest.

The present study is the first investigation of the inhibitory effect of Rhaponticum carthamoides transformed roots (TR) extract on the proliferation of grade II and III human glioma cells. TR extract showed the cytotoxic effect and inhibited the colony formation of both glioma cell lines in dose-dependent manner. The root extract induced apoptosis by increasing of the reactive oxygen species (about threefold compared to the control cells) leading to a disruption of mitochondrial membrane potential. Additionally, the mRNA levels of the apoptotic factors such as Bax, Tp53, caspase-3, and caspase-9 were observed to increase. These results indicate that the TR extract possesses anticancer activity by inhibiting glioma cell proliferation and inducing apoptotic cell death, and may be used as a promising anticancer agent.

Experiments on self-diffusion in amorphous silicon (Si) were performed at temperatures between 460 to 600° C. The amorphous structure was prepared by Si ion implantation of single crystalline Si isotope multilayers epitaxially grown on a silicon-on-insulator wafer. The Si isotope profiles before and after annealing were determined by means of secondary ion mass spectrometry. Isothermal diffusion experiments reveal that structural relaxation does not cause any significant intermixing of the isotope interfaces whereas self-diffusion is significant before the structure recrystallizes. The temperature dependence of self-diffusion is described by an Arrhenius law with an activation enthalpy Q=(2.70±0.11)  eV and preexponential factor D&#95;{0}=(5.5&#95;{-3.7}^{+11.1})×10^{-2}  cm^{2} s^{-1}. Remarkably, Q equals the activation enthalpy of hydrogen diffusion in amorphous Si, the migration of bond defects determining boron diffusion, and the activation enthalpy of solid phase epitaxial recrystallization reported in the literature. This close agreement provides strong evidence that self-diffusion is mediated by local bond rearrangements rather than by the migration of extended defects as suggested by Strauß et al. (Phys. Rev. Lett. 116, 025901 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.025901).

Electron microscopy images are interference patterns and can generally not be interpreted in a straight forward manner. Typically, time consuming numerical simulations have to be employed to separate specimen features from imaging artifacts. Directly comparing numerical predictions to experimental results, realistic simulation box sizes and varying imaging parameters are needed. In this work, we introduce an accelerated multislice algorithm, named STEMcl, that is capable of simulating series of large super cells typical for defective and amorphous systems, in addition to parameter series using the massive parallelization accessible in today's commercial PC-hardware, e.g. graphics processing units (GPUs). A new numerical approach is used to overcome the memory constraint limiting the maximum computable system size. This approach creates the possibility to study systematically the contrast formation arising by structural differences. STEM simulations of structure series of a crystalline Si and an amorphous CuZr system are presented and the contrast formation of vacancies/voids are studied. The detectability of vacancies/voids in STEM experiments is discussed in terms of density changes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Although active gonadotropin-secreting pituitary adenomas are considered very rare, the vast majority of pituitary tumours diagnosed as "non-functioning" express gonadotropins or their free β or α subunits. However, systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH), and α-subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking., Material and Methods: Immunostaining of FSH, LH, and αSU was compared in 43 surgically removed gonadotropin - expressing pitu-itary adenomas with serum concentrations of the above-mentioned substances before surgery in the same patients., Results: The serum concentrations of FSH were elevated (> 11.6 mU/mL) in 8/12 (66.7%) cases of FSH-positive adenomas. By contrast, in FSH-negative tumours the elevation of FSH is absent. Moreover, only 1/25 (4%) patients with LH-positive adenoma had the elevated serum concentration of LH (51.5 mU/mL). The overproduction of LH was not observed in adenomas expressing free β LH or in LH-negative tumours. In patients with αSU-positive adenomas elevated serum levels of αSU were observed in 3/15 (20%) cases. No αSU elevations were observed in patients with αSU-negative adenomas. The mean serum FSH, LH, and αSU concentrations were higher in patients with FSH, LH, and/or αSU immunopositive tumours in comparison with immunonegative. However, the differences are not statistically significant., Conclusions: Although "silent" gonadotropinomas constitute a frequent subtype of pituitary adenomas, the "active" subtype (i.e. manifesting by gonadotropin excess) are rare (approx. 4% of all pituitary adenomas). Gonadotropinomas are difficult to diagnose before surgery. The measurement of gonadotropins including αSU is needed but often not sufficient for presurgical diagnosis.

Background: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities., Materials and Methods: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed., Results: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757)., Conclusions: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

Crystalline and preamorphized isotope multilayers are utilized to investigate the dependence of ion beam mixing in silicon (Si), germanium (Ge), and silicon germanium (SiGe) on the atomic structure of the sample, temperature, ion flux, and electrical doping by the implanted ions. The magnitude of mixing is determined by secondary ion mass spectrometry. Rutherford backscattering spectrometry in channeling geometry, Raman spectroscopy, and transmission electron microscopy provide information about the structural state after ion irradiation. Different temperature regimes with characteristic mixing properties are identified. A disparity in atomic mixing of Si and Ge becomes evident while SiGe shows an intermediate behavior. Overall, atomic mixing increases with temperature, and it is stronger in the amorphous than in the crystalline state. Ion-beam-induced mixing in Ge shows no dependence on doping by the implanted ions. In contrast, a doping effect is found in Si at higher temperature. Molecular dynamics simulations clearly show that ion beam mixing in Ge is mainly determined by the thermal spike mechanism. In the case of Si thermal spike, mixing prevails at low temperature whereas ion beam-induced enhanced self-diffusion dominates the atomic mixing at high temperature. The latter process is attributed to highly mobile Si di-interstitials formed under irradiation and during damage annealing., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

This study determines the influence of transformed root (TR) extract of Leonurus sibiricus L. on various grades (I-III) of human glioma cells derived from patients. This plant occurs in southern Asia and Siberia and is widely used as a medicinal plant with various biological activities. Chromatographic profile of TR extract have revealed the presence of various polyphenolic compounds (4-hydroxybenzoic acid, gentisic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α-resorcylic acid). We found TR root extract to have antiproliferative activity on glioma cells after 24 h of treatment. TR root extract induces apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, enhanced S and G2/M phases of the cell cycle, and altered mRNA levels of Bax, Bcl-2, p53, Cas-3, Cas-8 and Cas-9 factors involved in apoptosis. This work for the first time demonstrate that TR extract from L. sibiricus root has the potential to activate apoptosis in grade I-III human glioma cells through the intrinsic and extrinsic pathways.

Introduction: Lack of efficacy of pharmacotherapy and physiotherapy in spinal pain syndrome is an indication for intervertebral stabilizer implantation between the processes in the lumbar segment of the spine., Material and Methods: The group consisted of 32 patients qualified after radioisotopic single-photon emission computed tomography/computed tomography (SPECT/CT) examinations with assessment of bone metabolism and mineral density. For comparative purposes, the L2 vertebra was defined as normal. Parameters defined in the area of operated vertebrae were comparable to L2. Imaging examinations and a pain intensity test were performed before and 12 months after the procedure., Results: In SPECT, osteotropic isotope (OI) activity in spinous bodies and processes was close to L2 values. Density assessed in CT of analysed vertebrae was close to L2. In the control examination, activity of OI in spinous bodies and processes was higher in the procedure area. Under the stabilizer, there was a strong positive correlation with the L2 parameters. The differences were statistically significant ( p = 0.0002). The increase of OI activity in the elements above the stabilizer was variable. In the control examination, there was higher density of spinous processes and bodies above and under the stabilizer. The difference, compared to the L2 density, was statistically significant., Conclusions: The radioisotopic method with SPECT/CT allows for the precise assessment of bone metabolism in the spine. After the procedure, a negative correlation was observed between bone metabolism changes and pain intensity test results., Competing Interests: The authors declare no conflict of interest.

Objective: The objective of this study was to determine the cytotoxic effect and apoptotic activity of Rhaponticum carthamoides transformed root (TR) and root of soil-grown plant (NR) extracts in a human glioma primary cells. The effect of these root extracts on cell cycle arrest, mitochondrial membrane potential (ΔΨm) and expression levels of apoptosis-related genes (Bcl-2, Bax and p53) were also examined., Methods: Cytotoxic activity of root extracts was evaluated by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Expression levels of apoptosis-related gene were analysed by RT-PCR and Western blotting. ΔΨm was examined by the use of JC-1 reagent., Key Findings: Rhaponticum carthamoides root extracts inhibit cell growth and induce apoptosis in a dose-dependent manner in human glioma cells. The root extracts were found to up-regulate the pro-apoptotic Bax protein and down-regulate the anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, an increase of the p53 protein level and reduction of ΔΨm in glioma cells were observed after treatment with NR and TR extracts., Conclusion: The results of this study may offer a new insight into the potential anticancer activity of R. carthamoides root extracts., (© 2016 Royal Pharmaceutical Society.)

Objective: The objective of this study is to assess the correlation between the degree of degeneration of lumbar discs according to the Pfirrmann classification system and the concentrations of metabolites determined by means of 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR) spectroscopy., Materials and Methods: Twenty-six human intervertebral lumbar discs that were operated on due to degenerative disease were analyzed. Routine preoperative 1.5T, T2-weighed magnetic resonance (MR) images were used to classify the cases according to the Pfirrmann classification system. In all the cases, during microdiscectomy, the fragments of the annulus fibrosus and nucleus pulposus were harvested and their metabolic profile was examined by means of 1H HR MAS. The grades of disc degeneration on the Pfirrmann scale were correlated with the metabolite concentrations., Results: Spectral analyses of the intervertebral discs with Pfirrmann grades IV and V demonstrated significantly higher concentrations of creatine, glycine, hydroxyproline, alanine, leucine, valine, acetate, isoleucine, α,β-glucose, and myo-inositol, and a lower intensity of the N-acetyl peak of chondroitin sulfate, compared to the spectra with Pfirrmann grade III., Conclusion: Our results demonstrate correlations between metabolite concentrations and the degree of lumbar disc degeneration assessed using the Pfirrmann grading system and provide another step toward the potential use of in vivo MR spectroscopy for investigation of biomarkers in lumbar disc degeneration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Arthrodesis of the knee joint is a mainly a salvage surgical procedure performed in cases of infected total knee arthroplasty, tumor, failed knee arthroplasty or posttraumatic complication.The authors report the case of 18-year-old male with posttraumatic complication of left knee because of motorbike accident 1 year before. He was treated immediately after the injury in the local Department of Orthopaedics and Traumatology. The examination in the day of admission to our department revealed deformation of the left knee, massive scar tissue adhesions to the proximal tibial bone and multidirectional instability of the knee. The plain radiographs showed complete lack of lateral compartment of the knee joint and patella. The patient complained of severe instability and pain of the knee and a consecutive loss of supporting function of his left limb. The authors decided to perform an arthroscopic-assisted fusion of the knee with Ilizarov external fixator because of massive scar tissue in the knee region and the prior knee infection.In the final follow-up after 54 months a complete bone fusion, good functional and clinical outcome were obtained.This case provides a significant contribution to the development and application of low-invasive techniques in large and extensive surgical procedures in orthopedics and traumatology. Moreover, in this case fixation of knee joint was crucial for providing good conditions for the regeneration of damaged peroneal nerve., Competing Interests: The authors declare no conflicts of interest.

Introduction: Non-functioning pituitary adenomas (NFPA) are often diagnosed late as invasive macroadenomas. The surgical resection is usually incomplete and about 50% of patients require additional surgery. Recent data suggest that somatostatin analogues (SSA), so important in the pharmacotherapy of acromegaly, can also be effective in the management of NFPA., Material and Methods: We analysed data of patients who had been treated up to 10 years previously with SSA: 40 with acromegaly (23 - primary, 17 - recurrent tumours) and 22 with NFPA (4 - primary, 18 - recurrent tumours). Hormonal profile, dynamics of tumour size change, ophthalmic syndromes, somatostatin receptor (SSTR) scintigraphy, and immunohistochemistry of SSTR subtypes of operated tumours as well as side effects were investigated., Results: Biochemical cure of acromegaly was achieved in 57.5% of patients, while reduction of tumour size was observed in 37% of patients and it was more frequent in not-operated cases. Regarding NFPA, stabilisation of tumour size was noticed in 68% of patients. Tumour shrinkage was reported in 9% of cases, but in 23% of the study group the adenoma size increased with indication for reoperation., Conclusions: The efficacy of SSA in NFPA is much lower in comparison to their well-established effects in the treatment of acromegaly. Stabilisation of tumour size, which is observed in the majority of NFPA, is significantly more frequent in comparison to the natural history of untreated NFPA and our previous studies as well. Analysis of SSTR subtypes is an argument in favour of introduction of novel broad-spectrum SSA that may be more effective in the treatment of NFPA. Referring to acromegaly, adenoma size decrease was reported more frequently in primary therapy. Considering recurrent tumours better outcomes were achieved in patients who were pre-treated with SSA before planned surgery. (Endokrynol Pol 2016; 67 (3): 292-298).

Introduction: The pituitary adenomas secreting thyrotropin (TSH) are considered the rarest type of hormonally active pituitary tumour. In spite of that, many cases are described in the literature. On the other hand, the observations of the co-expression of TSH with other pituitary hormones (mostly with growth hormone [GH]) and "silent" expression of TSH in clinically non-functioning pituitary adenomas (CNFPA) are rather scarce., Material and Methods: Among 93 examined pituitary adenomas, 22 of them were diagnosed as active acromegaly and 71 as clinically non-functioning pituitary adenomas (CNFPA). All of them were immunostained with antibodies against pituitary hormones, including the anti-TSH antibody. TSH-immunopositive adenomas are immunostained also to detect somatostatin receptor subtypes (SSTR 1-5)., Results: TSH immunopositivity was found in 4.2% of CNFPA (3/71 tumours) and in 13.6% (3/22) cases of somatotropinomas manifesting as active acromegaly. All of the examined TSH-immunopositive adenomas expressed SSTR subtypes except SSTR4. The symptoms of hyperthyroidism were not observed in any of the acromegalic patients co-expressing TSH with GH., Conclusions: Our data confirm the relative rarity of TSH expression or co-expression of TSH in pituitary tumours. In most cases TSH is co-expressed with GH in patients with acromegaly and is not accompanied by hyperthyroidism. The "silent" expression of TSH may occur also, although rarely in CNFPA. The strong expression of SSTR in TSH-immunopositive CNFPA ("silent thyrotropinoma") indicates the possibility of the treatment of these tumours with somatostatin analogues. (Endokrynol Pol 2016; 67 (5): 515-518).