Навчально-науковий медичний інститут (НН МІ)
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Item Invasive Breast Carcinoma of No Special Type with Medullary Pattern: Morphological and Immunohistochemical Features(Turkish Journal of Pathology, 2022) Линдін, Микола Сергійович; Lyndin, Mykola Serhiiovych; Гирявенко, Наталія Іванівна; Hyriavenko, Nataliia Ivanivna; Сікора, Владислав Володимирович; Sikora, Vladyslav Volodymyrovych; Линдіна, Юлія Миколаївна; Lyndina, Yuliia Mykolaivna; Soroka, Y.; Романюк, Анатолій Миколайович; Romaniuk, Anatolii MykolaiovychObjective: Our study investigated the morphological and immunohistochemical characteristics of invasive breast carcinoma of no special type (IBC-NST) with medullary pattern to explore the inconsistencies between the structural and clinical traits of this category of tumor. Material and Method: The breast carcinoma samples (n = 26) with medullary pattern (defined according to established criteria) were subjected to immunohistochemical assays of the following receptors: ER, PR, HER2/neu, Ki-67, p53, Bcl-2, VEGF, MMP1, E-cadherin, EGFR, Hsp70, Hsp90, CD20, CD3, CD4, CD8, CD68, CD163, CD56, CD138, MPO, S100, IgG, IgM, and PD-L1. Results: IBC-NST with medullary pattern was found to have negative expression of ER, PR, and HER2/neu; strong positive expression of Kі-67, mutant р53, Bcl-2, E-cadherin, EGFR, and PD-L1; moderate positive expression of Hsp70 and Hsp90; and low or negative expression of VEGF and MMP1. Furthermore, there was pronounced variability in the qualitative composition of tumor immune infiltrates with regards to T-lymphocytes, B-lymphocytes, macrophages, plasmocytes, and granulocytes. Conclusion: IBC-NST with medullary pattern has many unfavourable morphological and immunohistochemical prognostic characteristics, which are balanced against the pronounced protective properties of the tumor cells and the qualitative characteristics of the tumor microenvironment. These can lead to a favourable disease course despite the relatively adverse features of the carcinoma cells.Item Tumour microenvironment: Modulating effects, challenges, and future perspectives of oncolytic virotherapy in Astrocytoma treatment(Wolters Kluwer, 2022) Awuah, W.A.; Huang, H.; Kalmanovich, J.; Mehta, A.; Kundu, M.; Toufik, A.R.; Tanna, R.; Hasan, M.M.; Alexiou, A.; Сікора, Владислав Володимирович; Sikora, Vladyslav VolodymyrovychAstrocytomas are the most common type of glioma and arise from astrocytes, which are star-shaped cells found in the cerebrum. Depending on the severity, current therapy include surgical excision, fractionated radiation, chemotherapy, temozolomide, etc. Despite these treatments, the average 5-year survival rate for astrocytomas is only 5%. Oncolytic Virotherapy (OVT) provides a novel treatment that could increase this survival rate and employs viruses to infect and kill tumor cells. Though the use of OVT for malignant melanoma and gliomas in general is well documented, there is a lack of substantial literature to guide the therapeutic effects of OVT in astrocytomas.Item Embracing robotic surgery in low- and middle-income countries: Potential benefits, challenges, and scope in the future(Wolters Kluwer, 2022) Mehta, A.; Ng, J.C.; Awuah, W.A.; Huang, H.; Kalmanovich, J.; Agrawal, A.; Abdul-Rahman, T.; Hasan, M.M.; Сікора, Владислав Володимирович; Sikora, Vladyslav Volodymyrovych; Isik, A.Robotic surgery has applications in many medical specialties, including urology, general surgery, and surgical oncology. In the context of a widespread resource and personnel shortage in Low- and Middle-Income Countries (LMICs), the use of robotics in surgery may help to reduce physician burnout, surgical site infections, and hospital stays. However, a lack of haptic feedback and potential socioeconomic factors such as high implementation costs and a lack of trained personnel may limit its accessibility and application. Specific improvements focused on improved financial and technical support to LMICs can help improve access and have the potential to transform the surgical experience for both surgeons and patients in LMICs. This review focuses on the evolution of robotic surgery, with an emphasis on challenges and recommendations to facilitate wider implementation and improved patient outcomes.Item Telesurgery’s potential role in improving surgical access in Africa(Wolters Kluwer, 2022) Mehta, A.; Awuah, W.A.; Aborode, A.T.; Ng, J.C.; Candelario, K.; Vieira, I.M.P.; Bulut, H.I.; Abdul-Rahman,T.; Hasan, M.M.; Сікора, Владислав Володимирович; Sikora, Vladyslav VolodymyrovychAn estimated five billion people worldwide lack access to surgical care, while LMICs including African nations require an additional 143 million life-saving surgical procedures each year.African hospitals are under-resourced and understaffed, causing global attention to be focused on improving surgical access in the continent. The African continent saw its first telesurgery application when the United States Army Special Operations Forces in Somalia used augmented reality to stabilize lifethreatening injuries.Various studies have been conducted since the first telesurgery implementation in 2001 to further optimize its application.In context of a relative shortage of healthcare resources and personnel telesurgery can considerably improve quality and access to surgical services in Africa.telesurgery can provide remote African regions with access to knowledge and tools that were previously unavailable, driving innovative research and professional growth of surgeons in the region.At the same time, telesurgery allows less trained surgeons in remote areas with lower social determinants of health, such as access, to achieve better health outcomes. However, lack of stable internet access, expensive equipment costs combined with low expenditure on healthcare limits expansive utilization of telesurgery in Africa. Regional and international policies aimed at overcoming these obstacles can improve access, optimize surgical care and thereby reduce disease burden associated with surgical conditions in Africa.Item Approaching COVID-19 with epidemiological genomic surveillance and the sustainability of biodiversity informatics in Africa(Wiley, 2022) Aborode, A.T.; Huang, H.; Wireko, A. A.; Mehta, A.; Kalmanovich, J.; Abdul‐Rahman, T.; Сікора, Владислав Володимирович; Sikora, Vladyslav Volodymyrovych; Awaji, A.A.COVID‐19 is an acute respiratory illness caused by Severe Acute Respiratory Syndrome‐Coronavirus 2 (SARS‐CoV‐2). The first case was reported in Africa on February 14, 2020 and has surged to 11 million as of July 2022, with 43% and 30% of cases in Southern and Northern Africa. Current epidemiological data demonstrate heterogeneity in transmission and patient outcomes in Africa. However, the burden of infectious diseases such as malaria creates a significant burden on public health resources that are dedicated to COVID‐19 surveillance, testing, and vaccination access. Several control measures, such as the SHEF2 model, encompassed Africa's most effective preventive measure. With the help of international collaborations and partnerships, Africa's pandemic preparedness employs effective risk‐management strategies to monitor patients at home and build the financial capacity and human resources needed to combat COVID‐19 transmission. However, the lack of safe sanitation and inaccessible drinking water, coupled with the financial consequences of lockdowns, makes it challenging to prevent the transmission and contraction of COVID‐19. The overwhelming burden on contact tracers due to an already strained healthcare system will hurt epidemiological tracing and swift counter‐measures. With the rise in variants, African countries must adopt genomic surveillance and prioritize funding for biodiversity informatics.Item Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour(MDPI, 2022) Tucci, P.; Bove, M.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Dimonte, S.; Morgese, M.G.; Schiavone, S.; Di Cesare Mannelli, L.; Ghelardini, C.; Trabace, L.Glucoraphanin (GRA) is a natural compound that has shown beneficial effects in chronic diseases and in central nervous system disorders. Moreover, GRA displayed antidepressant activity in preclinical models. We have previously demonstrated that a single intracerebroventricular administration of soluble amyloid-beta 1-42 (sAβ 1-42) in rat evokes a depressive-like phenotype by increasing immobility frequency in the forced swimming test (FST). The aim of this work was to investigate the effect of GRA in naïve and in sAβ-1-42-treated rats by using the FST. Behavioural analyses were accompanied by neurochemical and biochemical measurements in the prefrontal cortex (PFC), such as serotonin (5-HT), noradrenaline (NA), kynurenine (KYN), tryptophan (TRP), reactive oxygen species (ROS) and the transcription nuclear factor kappa B (NF-kB) levels. We reported that GRA administration in naïve rats at the dose of 50 mg/kg reduced the immobility frequency in the FST and increased 5-HT and NA levels in the PFC compared to controls. At the same dose, GRA reverted depressive-like effects of sAβ 1-42 administration, restored the 5-HT levels and reduced NF-kB, KYN and ROS levels in PFC. In conclusion, GRA rapidly reverting depressive-like behaviour, together with biochemical and neurochemical alterations, might represent a safe and natural candidate for the treatment of depression.Item Social isolation triggers oxidative status and impairs systemic and hepatic insulin sensitivity in normoglycemic rats(Elsevier, 2022) Bove, M.; Lama, A.; Schiavone, S.; Pirozzi, C.; Tucci, P.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Trinchese, G.; Corso, G.; Morgese, M.G.; Trabace, L.Drug-naïve psychotic patients show metabolic and hepatic dysfunctions. The rat social isolation model of psychosis allows to investigate mechanisms leading to these disturbances to which oxidative stress crucially contributes. Here, we investigated isolation-induced central and peripheral dysfunctions in glucose homeostasis and insulin sensitivity, along with redox dysregulation. Social isolation did not affect basal glycemic levels and the response to glucose and insulin loads in the glucose and insulin tolerance tests. However, HOMA-Index value were increased in isolated (ISO) rats. A hypothalamic reduction of AKT phosphorylation and a trend toward an increase in AMPK phosphorylation were observed following social isolation, accompanied by reduced GLUT-4 levels. Social isolation also induced a reduction of phosphorylation of the insulin receptor, of AKT and GLUT-2, and a decreased phosphorylation of AMPK in the liver. Furthermore, a significant reduction in hepatic CPT1 and PPAR-α levels was detected. ISO rats also showed significant elevations in hepatic ROS amount, lipid peroxidation and NOX4 expression, whereas no differences were detected in NOX2 and NOX1 levels. Expression of SOD2 in the mitochondrial fraction and SOD1 in the cytosolic fraction was not altered following social isolation, whereas SOD activity was increased. Furthermore, a decrease of hepatic CAT and GSH amount was observed in ISO rats compared to GRP animals. Our data suggest that the increased oxidant status and antioxidant capacity modifications may trigger hepatic and systemic insulin resistance, by altering signal hormone pathway and sustaining subsequent alteration of glucose homeostasis and metabolic impairment observed in the social isolation model of psychosis.Item Ketamine administration in early postnatal life as a tool for mimicking Autism Spectrum Disorders core symptoms(Elsevier Inc., 2022) Bove, M.; Schiavone, S.; Tucci, P.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Dimonte, S.; Colia, A.L.; Morgese, M.G.; Trabace, L.Autism Spectrum Disorders (ASD) core symptoms include deficits of social interaction, stereotyped behaviours, dysfunction in language and communication. Beyond them, several additional symptoms, such as cognitive impairment, anxiety-like states and hyperactivity are often occurring, mainly overlapping with other neuropsychiatric diseases. To untangle mechanisms underlying ASD etiology, and to identify possible pharmacological approaches, different factors, such as environmental, immunological and genetic ones, need to be considered. In this context, ASD animal models, aiming to reproduce the wide range of behavioural phenotypes of this uniquely human disorder, represent a very useful tool. Ketamine administration in early postnatal life of mice has already been studied as a suitable animal model resembling psychotic-like symptoms. Here, we investigated whether ketamine administration, at postnatal days 7, 9 and 11, might induce behavioural features able to mimic ASD typical symptoms in adult mice. To this aim, we developed a 4-days behavioural tests battery, including Marble Burying, Hole Board, Olfactory and Social tests, to assess repetitive and stereotyped behaviour, social deficits and anxiety-like symptoms. Moreover, by using this mouse model, we performed neurochemical and biomolecular analyses, quantifying neurotransmitters belonging to excitatory-inhibitory pathways, such as glutamate, glutamine and gamma-aminobutyric acid (GABA), as well as immune activation biomarkers related to ASD, such as CD11b and glial fibrillary acidic protein (GFAP), in the hippocampus and amygdala. Possible alterations in levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus and amygdala were also evaluated. Our results showed an increase in stereotyped behaviours, together with social impairments and anxiety-like behaviour in adult mice, receiving ketamine administration in early postnatal life. In addition, we found decreased BDNF and enhanced GFAP hippocampal expression levels, accompanied by elevations in glutamate amount, as well as reduction in GABA content in amygdala and hippocampus. In conclusion, early ketamine administration may represent a suitable animal model of ASD, exhibiting face validity to mimic specific ASD symptoms, such as social deficits, repetitive repertoire and anxiety-like behaviour.Item Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity(Frontiers Media S.A., 2022) Morgese, M.G.; Bove, M.; Di Cesare Mannell, L.; Schiaone, S.; Coli, A.L.; Dimonte, S.; Mhillaj, E.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Tucci, P.; Ghelardini, C.; Traace, L.Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.Item Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity(Frontiers Media S.A., 2021) Morgese, M.G.; Bove, M.; Di Cesare Mannelli, L.; Schiavone, S.; Colia, A.L.; Dimonte, S.; Mhillaj, E.; Сікора, Владислав Володимирович; Сикора, Владислав Владимирович; Sikora, Vladyslav Volodymyrovych; Tucci, P.; Ghelardini, C.; Trabace, L.Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.