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Background: Osteoarthritis (OA) is a significant global health concern and is characterized by the degeneration of joint structures, leading to pain, stiffness, and functional limitations It is estimated that 654.1 million individuals are affected by osteoarthritis worldwide, with females, especially those older than 60 years of age, being the population most impacted. However, there remains a gap in understanding the awareness of knee osteoarthritis among specific populations, such as the Palestinian community in the West Bank, thus, highlighting the need for targeted research to address this health disparity., Methods: A cross-sectional survey was conducted in the West Bank from August to September 2024. Participants were recruited from 11 cities and a validated questionnaire adapted from a previous study was used to collect the data. The reliability of the questionnaire was assessed using Cronbach's alpha, yielding a value of standard alpha = 0.71, which is an acceptable value. The survey collected demographic data, clinical characteristics, knowledge of osteoarthritis risk factors, symptoms, and attitudes towards treatment options. R Statistical Software was used for data analysis, which included descriptive statistics, chi-square tests, and logistic regression to explore the relationships between demographic factors and osteoarthritis knowledge, whereby a p-value of ≤ 0.05 was set up as a significance level., Results: A total of 725 valid responses were included in our study. Among the participants, 569 were female, predominantly aged 25 or younger (66%, n = 479), and 62% (n = 450) were single. Knowledge assessment revealed that 80% (n = 580) recognized knee osteoarthritis as a chronic disease, while only 51% (n = 369) understood its impact on joint involvement. The majority identified high BMI (87%, n = 632), advancing age (94%, n = 683), and previous knee injury (72%, n = 520) as risk factors, although only 42% (n = 306) acknowledged genetics as one. Most participants were aware of the management strategies, including analgesics (70%, n = 510) and physiotherapy (80%, n = 579). However, 66% (n = 478) scored low for overall knowledge regarding knee osteoarthritis., Conclusion: This study emphasizes the critical importance of raising awareness and knowledge about osteoarthritis within the Palestinian community. Despite being widely known as a long-term issue, there are still noticeable gaps in the understanding of the joint impact, potential risks, and effective treatment methods for osteoarthritis. The use of informal sources highlights the importance of specific educational programs by healthcare providers., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Palestine Polytechnic University Ethics Committee, and it conformed to the ethics guidelines of the Declaration of Helsinki. All written consent was signed voluntarily and was obtained online. All adult subjects gave their permission to participate themselves. However, participants under 18 of age were automatically excluded. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

CNS tumours encompass a diverse group of neoplasms with significant morbidity and mortality. The SHH signalling pathway plays a critical role in the pathogenesis of several CNS tumours, including gliomas, medulloblastomas and others. By influencing cellular proliferation, differentiation and migration in CNS tumours, the SHH pathway has emerged as a promising target for therapeutic intervention. Current strategies such as vismodegib and sonidegib have shown efficacy in targeting SHH pathway activation. However, challenges such as resistance mechanisms and paradoxical effects observed in clinical settings underscore the complexity of effectively targeting this pathway. Advances in gene editing technologies, particularly CRISPR/Cas9, have provided valuable tools for studying SHH pathway biology, validating therapeutic targets and exploring novel treatment modalities. These innovations have paved the way for a better understanding of pathway dynamics and the development of more precise therapeutic interventions. In addition, the identification and validation of biomarkers of SHH pathway activation are critical to guide clinical decision making and improve patient outcomes. Molecular profiling and biomarker discovery efforts are critical steps towards personalised medicine approaches in the treatment of SHH pathway-associated CNS tumours. While significant progress has been made in understanding the role of the SHH pathway in CNS tumorigenesis, ongoing research is essential to overcome current therapeutic challenges and refine treatment strategies. The integration of molecular insights with advanced technologies and clinical expertise holds great promise for developing more effective and personalised therapies for patients with SHH pathway-driven CNS tumours., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval is not applicable. No original data from new patients were collected, consent to participate is not applicable. Consent for publication: Consent for publication is not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Whole-exome sequencing (WES), a ground-breaking technology, has emerged as a linchpin in neurology and neurosurgery, offering a comprehensive elucidation of the genetic landscape of various neurological disorders. This transformative methodology concentrates on the exonic portions of DNA, which constitute approximately 1% of the human genome, thus facilitating an expedited and efficient sequencing process. WES has been instrumental in advancing our understanding of neurodegenerative diseases, neuro-oncology, cerebrovascular disorders, and epilepsy by revealing rare variants and novel mutations and providing intricate insights into their genetic complexities. This has been achieved while maintaining a substantial diagnostic yield, thereby offering novel perspectives on the pathophysiology and personalized management of these conditions. The utilization of WES boasts several advantages over alternative genetic sequencing methodologies, including cost-effectiveness, reduced incidental findings, simplified analysis and interpretation process, and reduced computational demands. However, despite its benefits, there are challenges, such as the interpretation of variants of unknown significance, cost considerations, and limited accessibility in resource-constrained settings. Additionally, ethical, legal, and social concerns are raised, particularly in the context of incidental findings and patient consent. As we look to the future, the integration of WES with other omics-based approaches could help revolutionize the field of personalized medicine through its implications in predictive models and the development of targeted therapeutic strategies, marking a significant stride toward more effective and clinically oriented solutions., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval is not applicable. No original data from new patients were collected, consent to participate is not applicable. Consent for publication Consent for publication is not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Complications are plausible events during surgical operations. Surgical complications profoundly impact surgeons, often called "second victims" of adverse events. These complications trigger a range of emotional and psychological responses, including guilt, anxiety, heightened empathy, and the looming threat of burnout. Moreover, the toll extends to physical health, with chronic stress and sleep disturbances taking their toll. Surgeons' social lives are not immune to the fallout, and their career satisfaction may wane, pushing some towards defensive medicine practices. While mentorship, counselling, and peer support are crucial support mechanisms, they encounter barriers such as time constraints and the fear of negative perceptions. This paper suggests practical recommendations, including comprehensive wellness programmes, a streamlined badge card system for easy access to resources, and mindfulness training to mitigate stress and burnout. Recognising and proactively addressing these multifaceted impacts is imperative for cultivating a resilient medical community capable of providing optimal patient care., (© 2024. The Author(s).)

Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN's role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN's impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN's role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN's effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes., (© 2024. The Author(s).)

Ischaemic stroke, a leading cause of global morbidity and mortality, necessitates effective biomarkers for enhanced diagnostic and prognostic stratification. MicroRNAs (miRNAs), particularly miR-210, have emerged as promising candidates due to their intricate regulatory roles in cellular responses to hypoxia and neuroprotective effects. This study explores the potential of miR-210 as a biomarker for ischaemic stroke, considering its expression patterns, regulatory functions and diagnostic/prognostic implications. A literature search was conducted on PubMed, Scopus, Google Scholar and Web of Science to identify studies focusing on miR-210 in ischaemic stroke. Inclusion criteria comprised reports on miR-210 expression in ischaemic stroke patients, excluding non-English studies, reviews, commentaries and conference abstracts lacking primary data. Studies investigating miR-210 levels in ischaemic stroke patients revealed significant alterations in expression patterns compared to healthy controls. Diagnostic potential was explored, indicating miR-210's sensitivity and specificity in distinguishing ischaemic stroke from other neurological conditions. Prognostic value was evident through associations with infarct size, functional outcomes and long-term survival. Challenges included variability in miR-210 levels, limited diagnostic specificity, absence of standardised assays and concerns regarding cost-effectiveness and accessibility. While miR-210 holds promise as an ischaemic stroke biomarker, challenges must be addressed for its successful integration into clinical practice. Standardised reference ranges, validation studies in diverse populations and collaborative efforts for assay standardisation are crucial. Despite challenges, miR-210's diagnostic and prognostic potential, particularly in predicting therapeutic responses, suggests a significant role in advancing ischaemic stroke management., (© 2024. The Author(s).)

Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments., (© 2024. The Author(s).)

Background: Temporary abdominal closure (TAC) techniques are essential in managing open abdomen cases, particularly in damage control surgery. Skin-only closure (SC) and Bogota bag closure (BBC) are commonly used methods for TAC, but their comparative effectiveness in achieving primary fascial closure (PFC) remains unclear. The objective of this study was to evaluate the rates of PFC between patients undergoing SC and BBC techniques for TAC in peritonitis or abdominal trauma cases at a tertiary care hospital., Methods: A retrospective cross-sectional study was conducted at the Surgical A Unit of Hayatabad Medical Complex, Peshawar, from January 2022 to July 2023. Approval was obtained from the institutional review board, and patient consent was secured for data use. Patients undergoing temporary abdominal closure using either skin-only or Bogota bag techniques were included. Exclusions comprised patients younger than 15 or older than 75 years, those with multiple abdominal wall incisions, and those with prior abdominal surgeries. Data analysis utilized SPSS version 25. The study aimed to assess outcomes following damage control surgery, focusing on primary fascial closure rates and associated factors. Closure techniques (skin-only and Bogota bag) were chosen based on institutional protocols and clinical context. Indications for damage control surgery (DCS) included traumatic and non-traumatic emergencies. Intra-abdominal pressure (IAP) was measured using standardized methods. Patients were divided into SC and BBC groups for comparison. Criteria for reoperation and primary fascial closure were established, with timing and technique determined based on clinical assessment and multidisciplinary team collaboration. The decision to leave patients open during the index operation followed damage control surgery principles., Results: A total of 193 patients were included in this study, with 59.0% undergoing skin-only closure (SC) and 41.0% receiving Bogota bag closure (BBC). Patients exhibited similar demographic characteristics across cohorts, with a majority being male (73.1%) and experiencing acute abdomen of non-traumatic origin (58.0%). Among the reasons for leaving the abdomen open, severe intra-abdominal sepsis affected 51.3% of patients, while 42.0% experienced hemodynamic instability. Patients who received SC had significantly higher rates of primary fascial closure (PFC) compared to BBC (85.1% vs. 65.8%, p = 0.04), with lower rates of fascial dehiscence (1.7% vs. 7.6%, p = 0.052) and wound infections (p = 0.010). Multivariate regression analysis showed SC was associated with a higher likelihood of achieving PFC compared to BBC (adjusted OR = 1.7, 95% CI: 1.3-3.8, p < 0.05)., Conclusion: In patients with peritonitis or abdominal trauma, SC demonstrated higher rates of PFC compared to BBC for TAC in our study population. However, further studies are warranted to validate these results and explore the long-term outcomes associated with different TAC techniques., (© 2024. The Author(s).)

Background: Spinal ventral root avulsion results in massive motoneuron degeneration with poor prognosis and high costs. In this study, we compared different isoforms of basic fibroblast growth factor 2 (FGF2), overexpressed in stably transfected Human embryonic stem cells (hESCs), following motor root avulsion and repair with a heterologous fibrin biopolymer (HFB)., Methods: In the present work, hESCs bioengineered to overexpress 18, 23, and 31 kD isoforms of FGF2, were used in combination with reimplantation of the avulsed roots using HFB. Statistical analysis was conducted using GraphPad Prism software with one-way or two-way ANOVA, followed by Tukey's or Dunnett's multiple comparison tests. Significance was set at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001., Results: For the first set of experiments, rats underwent avulsion of the ventral roots with local administration of HFB and engraftment of hESCs expressing the above-mentioned FGF2 isoforms. Analysis of motoneuron survival, glial reaction, and synaptic coverage, two weeks after the lesion, indicated that therapy with hESCs overexpressing 31 kD FGF2 was the most effective. Consequently, the second set of experiments was performed with that isoform, so that ventral root avulsion was followed by direct spinal cord reimplantation. Motoneuron survival, glial reaction, synaptic coverage, and gene expression were analyzed 2 weeks post-lesion; while the functional recovery was evaluated by the walking track test and von Frey test for 12 weeks. We showed that engraftment of hESCs led to significant neuroprotection, coupled with immunomodulation, attenuation of astrogliosis, and preservation of inputs to the rescued motoneurons. Behaviorally, the 31 kD FGF2 - hESC therapy enhanced both motor and sensory recovery., Conclusion: Transgenic hESCs were an effective delivery platform for neurotrophic factors, rescuing axotomized motoneurons and modulating glial response after proximal spinal cord root injury, while the 31 kD isoform of FGF2 showed superior regenerative properties over other isoforms in addition to the significant functional recovery., (© 2024. The Author(s).)

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs., (© 2024. The Author(s).)

Using the particular nature of melanoma mutanomes to develop medicines that activate the immune system against specific mutations is a game changer in immunotherapy individualisation. It offers a viable solution to the recent rise in resistance to accessible immunotherapy alternatives, with some patients demonstrating innate resistance to these drugs despite past sensitisation to these agents. However, various obstacles stand in the way of this method, most notably the practicality of sequencing each patient's mutanome, selecting immunotherapy targets, and manufacturing specific medications on a large scale. With the robustness and advancement in research techniques, artificial intelligence (AI) is a potential tool that can help refine the mutanome-based immunotherapy for melanoma. Mutanome-based techniques are being employed in the development of immune-stimulating vaccines, improving current options such as adoptive cell treatment, and simplifying immunotherapy responses. Although the use of AI in these approaches is limited by data paucity, cost implications, flaws in AI inference capabilities, and the incapacity of AI to apply data to a broad population, its potential for improving immunotherapy is limitless. Thus, in-depth research on how AI might help the individualisation of immunotherapy utilising knowledge of mutanomes is critical, and this should be at the forefront of melanoma management., (© 2023. The Author(s).)

Background: The Russia-Ukraine war has undeniably impacted global science and healthcare in Ukraine. Many Ukrainian researchers have had their projects disrupted by this war, either due to loss of life, displacement, or destruction of resources. Despite these challenges, these researchers have sought to make their voices heard. This scoping review highlights the trend of healthcare-related publications on the current Russia-Ukraine war and characterizes the contribution of Ukrainian authors to these publications., Method: A comprehensive literature search was performed using two databases (Scopus and Pubmed) for publications related to the ongoing Russia-Ukraine war. We included articles only related to healthcare. We then extracted and analyzed bibliometric data., Result: One hundred and eighty-three articles were identified, including 12 (6.6%) original articles, 26 (14.2%) cross-sectional studies, 19 (10.4%) letters to the editor, 10 (5.5%) commentaries, 5 (2.7%) perspectives, 35 (19.1%) editorials, 2 (1.1%) randomized controlled trials, 11(6.0%) correspondences, 13 (7.1%) opinions, 8 (4.4%) reviews and 42 (23.0%) are identified as others. 180 (98.4%) studies were in English, and 3 (1.7%) were in German. 54 (29.5%) papers on the war had at least one author affiliated with a Ukrainian institution, and 29 (15.9%) studies had authors with Ukrainian affiliation as first authors., Conclusion: our study shows that there has been a significant number of publications on the Russia-Ukraine war and only a small portion of first authors, co-authors, and last authors of these publications are affiliated to an institution in Ukraine. Therefore, despite the relatively high number of publications, most publications do not arise from the perspective of Ukrainian authors., (© 2023. The Author(s).)

Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes., (© 2023. The Author(s).)

Background: The Biopsychosocial (BPS) model is recognized and widely accepted in the field of health care, particularly in rehabilitation. However, in clinical practice the applicability of the BPS model is a challenge for many professionals., Method: This study aimed to explore the factors that impact the perception of rehabilitation professionals about the BPS model in Ukraine. In addition, the job satisfaction assessment was done to measure whether rehabilitation specialists in Ukraine fulfil their professional roles according to their expectations and values. Participants were 346 rehabilitation specialists from Ukraine who completed the Bio-Psycho-Social Scale (BPS) for Use in Healthcare and the Global Job Satisfaction Scale (GJSS). The ANOVA was used to investigate the outcome differences between the two scales., Results: The highest proportion of responders in this study represented state health services. The BPS subscale outcomes on "assessment and reporting" and "professional knowledge and skills" were significantly higher for specialists from a private sector. The global job satisfaction scale outcomes did not differ between responders from the private and state health sector. The perception of professionals networks was associated with greater job satisfaction., Conclusions: The findings suggest that conception of the BPS approach in rehabilitation system of Ukraine varies across the private and state settings. The professional network plays important role in job satisfaction of rehabilitation professionals in Ukraine. Future research focusing on education strategies to effectively train professionals to apply biopsychosocial approach to practice is of critical importance to prepare rehabilitation specialists in Ukraine., (© 2022. The Author(s).)

Background: The purpose of this study is to forward the implementation of an operational evidence-based state screening program of common diseases in Ukraine, where currently no state-based and evidence-based screening (EBS) exists. EBS should be performed by Family Doctors in a primary care setting and concern prevalent diseases in adults, such as: obesity (BMI), hypertension (BP measurement), diabetes (glycaemia), dyslipidemia (cholesterol/lipids), colon cancer (FOBT/colonoscopy), breast cancer (mammography), STIs (chlamydia, syphilis), HIV, HBV, HCV (i.e. serology or other rapid tests), HPV (swabs), cervical cancer (test Pap). depression (i.e., PHQ-9), and smoking (i.e., Fagerstrom)., Methods: Four needs-based research actions were led among citizens and healthcare professionals, based on multidimensional empowerment. Internal Strengths and Weaknesses of the ongoing implementation process were identified through these studies, whereas external Opportunities and Threats were determined by the present socio-cultural and political context. This SWOT analysis is likely to guide future state-based initiatives to accomplish EBS implementation in Ukraine., Results: Internal Strengths are the bottom-up multidimensional empowerment approach, teaching of EBS and the development of an internet-based platform "Screening adviser" to assist shared decision making for person-centred EBS programs. Internal Weaknesses identified for the Family Doctors are a heterogeneous screening and the risk of decreasing motivation to screen. External Opportunities include the ongoing PHC reform, the existent WONCA and WHO support, and the existence of EBS programs in Europe. External Threats are the lack of national guidelines, not fully introduced gate keeping system, the vulnerable socio-economic situation, the war situation in the East of Ukraine and the Covid-19 pandemic., Conclusions: We started EBS implementation through research actions, based on a multidimensional empowerment of citizens, HCP and in EBS pathways involved stakeholder teams, to foster a sustainable operational human resource to get involved in that new EBS pathway to implement. The presented SWOT-analysis of this ongoing implementation process allows to plan and optimize future steps towards a state based and supports EBS program in Ukraine.

Background: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of α-synuclein (α-syn) and S100A9 both in vitro and ex vivo in PD brain., Methods: Single and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and α-syn location and aggregation. In vitro studies revealing S100A9 and α-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods., Results: Co-localized and co-aggregated S100A9 and α-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 μm outer diameter, with S100A9 and α-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and α-syn were shown to interact with each other via the α-syn C-terminus with an apparent dissociation constant of ca. 5 μM. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of α-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers., Conclusions: We suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving α-syn and S100A9 and leading to PD, similar to the effect of S100A9 and Aβ co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.

Background: Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia. The impressive rates of industrial development led to the pollution of soil, surface water and, as a consequence, food by heavy metal salts.The purposes of this paper are as follows: the chemical composition determination of neoplastic breast tissue, evaluation of the DNA methylation level, study of prognostic-important receptors expression in the breast cancer cells, establishing linkages between all the derived indicators., Methods: In our study we used the following methods: studying of the chemical composition of breast cancer tissue by atomic absorption spectrophotometry and energy-dispersion spectrometer; іmmunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E-cadherin and MGMT receptors; DNA extraction and investigation by oscillating infrared spectroscopy method., Results: The total amount of heavy metals in breast cancer tissue ranged from 51.21 × 10 -3 to 84.86 × 10 -3  μg/kg. We have got the following results: the growth of heavy metals in neoplastic tissue is accompanied with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and PR expression. The increment of pathological DNA methylation is accompanied with the increasing amount of heavy metals in tumor tissue., Conclusions: Heavy metals through different pathogenetic links stimulate the progression of breast cancer and reduce its sensitivity to treatment. DNA of tumor tissue has a different level of methylation which changes with the amount of heavy metals in cancer cells. This is displayed on the synthesis of prognostically important receptors in neoplastic tissue.

Background: Periodontal inflammation is characterized by injuries in collagen, epithelial, bone tissues. The hypotheses to be tested were relationship between the s100, bcl2 and myeloperoxidase in gingival tissues (MPO does affect the level of s100, bcl2). The object of this study was to investigate of s100 expression, bcl2 expression and myeloperoxidase expression in periodontal inflammation., Methods: 27 patients (giant-cell epulis) and 30 patients (acute and chronic inflammations) were included in the study for s100 expression, bcl2 expression and myeloperoxidase expression by immunohistochemistry and hematoxylin--eosin., Results: Giant-cells in epulis positivity for myeloperoxidase has been observed in 100% However, only 75.31% of giant-cells were positive for bcl2 expression. Acute 98.2%, and chronic 89.28% inflammation was a significant positive for myeloperoxidase. The immunohistochemical findings of s100, bcl 2 and myeloperoxidase in epithelial layers have showed the result of 100%, 82,2%, 100% positive cells in acute and 100%, 78.25%, 100% in chronic process of inflammation respectively., Conclusion: The results indicate that the pathogenesis of periodontal inflammation might involve inhibition of cell death, through the overexpression of bcl-2, due to identifying factors myeloperoxidase (result in the DNA damage by the product of catalysis). The highest levels of s100 activity have been found at sites with chronic inflammation.

Background: The rate of progression of the disease depends on various factors and the tumor microenvironment takes not the last place among them. One part of researchers argues that the presence of tumor-infiltrating leukocytes serves as a favorable marker of the disease. There exists a completely different point of view on the matter. The investigation of the effects of the inflammatory infiltration on the course of breast cancer process., Methods: We found a pronounced inflammatory infiltration in the tumor microenvironment in 24 cases. Nineteen cases of IDC without inflammatory infiltration were used as a control group. Immunohistochemical reaction showed expression of ERα, PR, HER2/neu, E-cadherin, Hsp90α, Bcl-2, CD3, CD79α, S100 and Myeloperoxidase receptors. Mathematical calculations were done using Microsoft Excel 2010 with 12.0.5 Attestat option., Results: We have determined five variants of immune microenvironment: interstitial, trabecular, nodular, diffuse and mixed. We have established a direct correlation between the expression of ERα and PR and indirect correlation between the receptors of steroid hormones and HER2/neo in both groups of breast cancer. HER2/neo positive tumors in 100% of cases were accompanied by the presence of heat shock proteins. There was a combination of Bcl-2 presence with the steroid receptors expression in 90 % of cases. There was found the indirect correlation between the presence of B lymphocytes and expression of steroid receptors., Conclusions: The presence of B lymphocytes in an inflammatory infiltrate leads to the disappearance of estrogen receptors and progesterone receptors. It provokes the accumulation of Hsp90 in a cell. It contributes to the stabilization of HER2/neu receptors and most proteins that promote tumor progression., Virtual Slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1362330168161694.