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The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

BackgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.Methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.ResultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.ConclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provokinghemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

This study explores the childhood experiences and transitions to adulthood of 39 Romanian care leavers and adoptees, born around 1989 - 1990. In the past, Romania’s children in care became known to the world as 'the Romanian orphans' and some of them have been subjects to neurodevelopmental research studies focusing on the setbacks posed by institutionalisation in early life. This research project takes a different angle by: • Using life history approach and therefore capturing the participants’ in-depth accounts of how they recall their childhoods and the challenges they encountered in their transition to independent life; • Exploring four different types of placements and how they affect transition to independent life, from a user’s perspective. The fact that Romania undertook reform of the child protection system within the timespan of this generation of children provided a research opportunity to collect the users’ views on different types of placement that belonged to the unreformed system of the 1990s (large residential care and intercountry adoption) and the new types of placement (small group homes and foster care). For comparison purposes, I also included domestic adoption, a type of placement that was less controversial than the others at the time reforms were being introduced. Thus, the types of placement that are analysed through the research participants’ accounts are: • Residential care (institutions and small group homes) • Foster Care • Domestic Adoption • Intercountry adoption The study addressed two research questions: 1. How do Romanian born young people who grew up in care understand and narrate their experiences in different types of placement? 2. What narratives of agency are constructed by Romanian-born adults who grew up in different types of placement when they describe their transition to adulthood? By taking an interpretive stance, this study brings in the academic arena the voices of care leavers and adoptees. By using narrative analysis and focussing on the concept of dignity by employing identity theories, the UN Convention on the Rights of the Child and the Capabilities Approach, the study makes an important contribution to knowledge, with implications for further research, policy and practice. While interventions in child protection are influenced in each country by cultural, political and socio-legal factors, understanding the basic needs of children who are not raised by their birth families is important across different child protection systems. Therefore, the relevance of the research findings is not limited to Romania.

Human papilloma viruses (HPV) are a small group of non-enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double-stranded DNA, encompassing eight open reading frames, as well as a non-enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High-risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre-cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti-papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.

Non-melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun-protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun-exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. Aside from the well-known etiopathogenic factors, studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with the exception of penile SCC, for which a paucity of specific data on their pathogenic role exists. The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene-related peptide and somatostatin, as well as neurohormones, such as proopiomelanocortin and its derived peptides, α-melanocyte-stimulating hormone and adrenocorticotropin. All these factors have been, at least at some point, a subject of debate regarding their precise role in the pathogenesis of NMSC. There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC. Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. Further studies are required in order to elucidate the exact mechanisms through which neuroactive molecules promote or inhibit cutaneous carcinogenesis, as this could lead to the development of more sophisticated and tailored treatment protocols, as well as open new perspectives in skin cancer research.

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 x acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 x ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

Capsaicin induces a localized inflammatory process known as neurogenic inflammation upon its topical administration on the skin, due to the release of various neuropeptides from the cutaneous sensory nerve endings. In this study, we investigated real-time skin blood flow changes that occur in neurogenic inflammation induced by topical capsaicin by means of in vivo reflectance confocal microscopy. 27 healthy subjects (15 women and 12 men, mean age ± Standard Deviation: 22.62±4.47) were administered topical capsaicin solution (Capsaicin group) or immersion oil (Control group) on the dorsal side of their non-dominant hand. At different time intervals during administration (0, 10, 25, and 40 minutes), cutaneous blood flow was evaluated using reflectance confocal microscopy and compared between the two groups. Blood flow values were higher during topical capsaicin, with significant increase after 25 (P=0.0160, Dunn’s multiple comparisons test) and 40 minutes (P=0.0132, Dunn’s multiple comparisons test) after its administration when compared with the initial 0 min value. Furthermore, the differences in the blood flow changes between the two groups were significant at 25 min (P=0.0182, Dunn’s multiple comparisons test) and 40 min (P=0.0296, Dunn’s multiple comparisons test) after capsaicin administration. Reflectance confocal microscopy allows in vivo, real-time evaluation of cutaneous blood flow changes within the capsaicin-induced inflammation, and this method might serve as a research model to test neurovascular reactivity.

Maria Linda Cruceru,1 Ana-Maria Enciu,1,2,7 Adrian Claudiu Popa,1,3 Radu Albulescu,2,4,7 Monica Neagu,2,7 Cristiana Pistol Tanase,2,7 Stefan N Constantinescu5–7 1Carol Davila University of Medicine and Pharmacy, Department of Cellular and Molecular Medicine, Bucharest, Romania; 2Victor Babes National Institute of Pathology, Bucharest, Romania; 3Army Centre for Medical Research, Bucharest, Romania; 4National Institute for Chemical Pharmaceutical R&D, Bucharest, Romania; 5de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; 6Ludwig Institute for Cancer Research, Brussels, Belgium; 7Operational Sectorial Programme for Competitive Economic Growth Canbioprot at Victor Babes National Institute of Pathology, Bucharest, Romania Purpose: The expression of an array of signaling molecules, along with the assessment of real-time cell proliferation, has been performed in U87 glioma cell line and in patients’ glioblastoma established cell cultures in order to provide a better understanding of cellular and molecular events involved in glioblastoma pathogenesis. Experimental therapy was performed using a phosphatydylinositol-3´-kinase (PI3K) inhibitor. Patients and methods: xMAP technology was employed to assess expression levels of several signal transduction molecules and real-time xCELLigence platform for cell behavior. Results: PI3K inhibition induced the most significant effects on global signaling pathways in patient-derived cell cultures, especially on members of the mitogen-activated protein-kinase family, P70S6 serine-threonine kinase, and cAMP response element-binding protein expression and further prevented tumor cell proliferation. Conclusion: The PI3K pathway might be a prime target for glioblastoma treatment. Keywords: personalized medicine, PI3K inhibitor, targeted therapy, xCELLigence, xMAP analysis

The present paper reopens the discussion over several antropomorphic figurines found during the excavations on the Vidra tell. The figurines are part of the collection of the Bucharest City Museum (MMB). The majority of them were assigned by the author of the excavations, D. V. Rosetti, to the B1 phase of the Gumelnitsa culture. The exact archaeological context of the figurines is unknown. The authors used for the study of this lot a relatively recent method of investigation – the X-ray tomography. The X-ray equipment was specifically built for applications in archaeology and is unique in Romania. The X-ray tomography proved to be a very useful tool in archaeological research and cultural heritage studies, presenting a series of advantages

With the expansion of the nanomedicine field, the knowledge focusing on the behavior of nanoparticles in the biological milieu has rapidly escalated. Upon introduction to a complex biological system, nanomaterials dynamically interact with all the encountered biomolecules and form the protein “bio-corona.” The decoration with these surface biomolecules endows nanoparticles with new properties. The present review will address updates of the protein bio-corona characteristics as influenced by nanoparticle’s physicochemical properties and by the particularities of the encountered biological milieu. Undeniably, bio-corona generation influences the efficacy of the nanodrug and guides the actions of innate and adaptive immunity. Exploiting the dynamic process of protein biocorona development in combination with the new engineered horizons of drugs linked to nanoparticles could leadto innovative functional nanotherapies. Therefore, bio-medical nanotechnologies should focus on the interactions of nanoparticles with the immune system for both safety and efficacy reasons

The incidence of human papillomavirus (HPV) in the human cancer domain is still a subject of intensive study. In this study, we examined cervical swab samples from 713 females with genital warts, and tested the samples for high‑and low‑risk genital HPV. HPV genotyping was assessed using a Genotyping test that detects HPV by the amplification of target DNA using polymerase chain reaction and nucleic acid hybridization. In total, we detected 37 anogenital HPV DNA genotypes [6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73 (MM9), 81, 82 (MM4), 83 (MM7), 84 (MM8), IS39 and CP6108] and investigated the incidence of these genotypes in the patients with genital warts. We found differences in the distribution of high‑/low‑risk strains and the incidence of high‑risk strains was found to occur mainly in females under 35 years of age. The data from our study suggest that a detailed oral, rectal and genital identification of high‑risk strains should be performed to visualize the entire pattern of possible triggers of carcinogenesis. © 2016, Spandidos Publications. All rights reserved.

Reflectance-mode confocal microscopy (RCM) is a new in vivo skin imaging technique. We present our one-year experience in RCM examinations in skin tumors and the retrospective analysis of patients enrolled in the Dermatological Department of 'N. Paulescu' Institute using the Fotofinder Dermoscope IIŴ for the dermatoscopy analysis and VivaScope 1500Ŵ for in vivo RCM. We established the rank of RCM in the complex algorithm of skin cancer diagnose, showing that the presented experience can open new possibilities to implement this automated image analyzing system in the routine practice. Our analyzed cases clearly showed that confocal microscopy, therefore, optical biopsy, could guide the clinician towards an accurate diagnosis before surgical removal. Moreover, we emphasized that the development of this technique increases the potential of future teledermatologic applications.

Neutrophils are short-lived leukocytes and major components of the innate immune system. They are key players in the body's defense against pathogens, but their contribution to tumor growth and metastasis is controversial. Nevertheless, improving the functions of neutrophils in cancer patients, particularly in those undergoing chemotherapy, is of clinical significance. In this study, we investigated the ability of the immunoreactive fragment of the polypeptide prothymosin alpha (proTα), i.e., the decapeptide proTα(100-109), to enhance the functions of neutrophils isolated from the peripheral blood of breast cancer patients in comparison with those from healthy donors. Activation of neutrophils from both groups with proTα(100-109) significantly increased phagocytosis and the production of intracellular reactive oxygen species (ROS) compared to controls. The release of extracellular ROS and oxidative burst of proTα(100-109)-stimulated neutrophils were less improved. Most importantly, upon activation with proTα(100-109), neutrophils from breast cancer patients showed significantly enhanced cytotoxicity against tumor cell targets. Using a scrambled peptide as a control, we showed that the proTα(100-109)-induced effects were sequence-specific and comparable to those exerted by the parental molecule proTα. The responsiveness of neutrophils to proTα(100-109) or intact proTα did not correlate with the tumor grade or other established tumor characteristics. Our results suggest that proTα(100-109) activates neutrophils, particularly those derived from breast cancer patients, and these effects could potentially be used to improve some functions of neutrophils in the clinical setting. © 2012 Elsevier B.V. All rights reserved.

Using the pulsed laser ablation technique, Fe73.5Cu1Nb3Si15.5B7 amorphous thin films, with smooth and uniform surfaces, have been deposited on glass and silicon substrates. Based on the information provided by the thermomagnetic analysis, the nanocrystalline state was achieved after the thermal treatment per-formed at 460 C. In nanocrystalline state, the samples present an 80 % lower coercive magnetic field and a 3.5 times higher saturation magnetization with respect to the as-deposited state. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/35150

The aim of this paper is to develop on the 1-jet space J^1(R,M^4) the jet Generalized Lagrange Geometry for the rheonomic Chernov metric. The associated gravitational and electromagnetic field models based on the rheonomic Finsler Chernov metric tensor are developed and discussed., Comment: 14 pages

Prothymosin α (proTα) is a 109 amino acid long polypeptide presenting distinct immunoenhancing activity in vitro and in vivo. Recent reports suggest that in apoptotic cells, proTα is cleaved by caspases at its carboxy(C)-terminus generating potentially bioactive fragments. In this study, we identified the peptide segment of proTα presenting maximum immunomodulatory activity. Calf thymus proTα was trypsinised, and the five fragments produced (spanning residues 1-14, 21-30, 31-87, 89-102 and 103-109) were tested for their ability to stimulate healthy donor- and cancer patient-derived peripheral blood mononuclear cell (PBMC) proliferation in autologous mixed lymphocyte reaction (AMLR), natural killer and lymphokine-activated killer cell activity, intracellular production of perforin, upregulation of adhesion molecules and CD25 expression. ProTα(89-102) and proTα(103-109) significantly fortified healthy donor-lymphocytes' immune responses to levels comparable to those induced by intact proTα. These effects were more pronounced in cancer patients, where peptides proTα(89-102) and proTα(103-109) partly, however significantly, restored the depressed AMLR and cytolytic ability of PBMC, by simulating the biological activity exerted by intact proTα. ProTα(1-14), proTα(21-30) and proTα(31-87) marginally upregulated lymphocyte activation. This is the first report showing that proTα's immunomodulating activity can be substituted by its C-terminal peptide(s). Whether generation and externalization of such immunoactive proTα fragments occurs in vivo, needs further investigation. However, if these peptides can trigger immune responses, they may eventually be used therapeutically to improve some PBMC functions of cancer patients. © Springer-Verlag 2006.