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The article carries out a scientific and practical analysis of the terms used by the legislator in the disposition of Article 436-2 of the Criminal Code of Ukraine, and which, in fact, are an innovation in the science of criminal law of Ukraine. In particular, the author's interpretation of such forms of the objective side of the above-mentioned criminal offense as "justification", "recognition as legitimate", "denial", "glorification" is given. In addition, the authors carried out: substantiation from the point of view of domestic legislation and international law of the facts of the armed aggression of the russian federation against Ukraine, which began in 2014, and the temporary occupation of part of the territory of Ukraine; understanding the general reasons for the criminalization of actions that form the objective side of the criminal offense provided for in Art. 436-2 of the Criminal Code of Ukraine; consideration of the above terms in their general meaning and in the meaning determined by the context of criminal liability. The non-acceptance of the obvious fact that the military-political leadership of the russian federation launched an aggressive war against our country and occupied part of the territories, when this fact was established and recognized at the state level and by the international community, in the conditions of martial law, is, on the one hand, a prerequisite for collaborative activities within the state, and on the other hand, to the support of the crime of aggression by representatives of other states. Justification, recognition as legitimate, denial of the armed aggression of the russian federation against Ukraine, glorification of its participants are part of the information war of the russian federation against Ukraine, aimed at leveling the external grounds for repelling the armed aggression of the terrorist country, as well as preventing society from rallying around a national strategy of unity to repel threats to the national statehood, territorial integrity and inviolability of Ukraine. Despite the fact that since the introduction of criminal liability for the above-mentioned acts, enough time has passed for the formation of judicial and investigative practice of bringing people to criminal liability, the theoretical basis for the interpretation of certain terms has not yet been created. In general, the scientific conclusions obtained in the article can be the beginning of the formation of such a foundation.

The SARS-CoV-2 global pandemic has seen rapid spread, disease mobidities and death associated with substantive social, economic and societal impact. Treatments rely on re-purposed antivirals and immune modulatory agents focusing on attenuating the acute respiratory distress syndrome. No curative therapies exist. Vaccines remain the best hope for disease control and elimination and the principal global effort with success now being realized. Herein, we summarize those developments with a focus on the role played by nanocarrier delivery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large.

Graphical abstract The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2, is a positive-sense single-stranded RNA virus with epithelial cell and respiratory system proclivity. Like its predecessor, SARS-CoV, COVID-19 can lead to life-threatening disease. Due to wide geographic impact affecting an extremely high proportion of the world population it was defined by the World Health Organization as a global public health pandemic. The infection is known to readily spread from person-to-person. This occurs through liquid droplets by cough, sneeze, hand-to-mouth-to-eye contact and through contaminated hard surfaces. Close human proximity accelerates SARS-CoV-2 spread. COVID-19 is a systemic disease that can move beyond the lungs by blood-based dissemination to affect multiple organs. These organs include the kidney, liver, muscles, nervous system, and spleen. The primary cause of SARS-CoV-2 mortality is acute respiratory distress syndrome initiated by epithelial infection and alveolar macrophage activation in the lungs. The early cell-based portal for viral entry is through the angiotensin-converting enzyme 2 receptor. Viral origins are zoonotic with genomic linkages to the bat coronaviruses but without an identifiable intermediate animal reservoir. There are currently few therapeutic options, and while many are being tested, although none are effective in curtailing the death rates. There is no available vaccine yet. Intense global efforts have targeted research into a better understanding of the epidemiology, molecular biology, pharmacology, and pathobiology of SARS-CoV-2. These fields of study will provide the insights directed to curtailing this disease outbreak with intense international impact. Graphical Abstract.

Graphical Abstract Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs’ as a vaccine candidate delivery system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large.

Aberrant methylation of gene promoter regions is the main epigenetic change characterizing colorectal cancer. Methylation levels of 42 CpG-sites of promoter regions of the MGMT, APC and CDH13 genes in colorectal cancer were studied in comparison with methylation levels of the adjacent normal tissue in 25 patients. Pyrosequencing showed an increase in methylation levels of promoter regions of the MGMT, APC and CDH13 genes in tumor samples by 3 to 5 times. These tumor samples were screened for activating SNP-mutations in the KRAS (40 %), NRAS (0 %) and BRAF (0 %) oncogenes. SNP-mutations in the KRAS gene were accompanied by hypermethylation of one or more promoters of the studied genes. Association of this epigenetic index with tumor metastasis was proved. The data on an increase in methylation of the promoter regions of oncosupressor genes can be used as sensitive prognostic markers of progression and metastasis of colorectal cancer.

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, limitations in drug efficacy, emergence of viral mutations and the paucity of cell-tissue targeting remain. We posit that to maximize ART potency and therapeutic outcomes newer drug formulations that reach HIV cellular reservoirs need be created. In a step towards achieving this goal we harnessed the aggregation-induced emission (AIE) property of the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV) and used it as a platform for drug cell and subcellular tracking. RPV nanocrystals were created with endogenous AIE properties enabling the visualization of intracellular particles in cell and tissue-based assays. The intact drug crystals were easily detected in CD4+ T cells and macrophages, the natural viral target cells, by flow cytometry and ultraperformance liquid chromatography tandem mass spectrometry. We conclude that AIE can be harnessed to monitor cell biodistribution of selective antiretroviral drug nanocrystals.

The utility of mesh reinforcement for small hiatal hernia found especially during antireflux surgery is unknown. Initial reports for the use of biological mesh for crural reinforcement during repair for defects greater than 5 cm have been shown to decrease recurrence rates. This study compares patients with small hiatal hernias who underwent onlay biologic mesh buttress repair versus those with suture cruroplasty alone. This is a single-institution retrospective review of all patients undergoing repair of hiatal hernia measuring 1-5 cm between 2002 and 2009. The patients were evaluated based on surgical repair: one group undergoing crural reinforcement with onlay biologic mesh and other group with suture cruroplasty only. Seventy patients with hiatal hernia measuring 1-5 cm were identified. Thirty-eight patients had hernia repair with biologic mesh, and 32 patients had repair with suture cruroplasty only. Recurrence rate at 1 year was 16% (5/32) in patients who had suture cruroplasty only and 0% (0/38) in the group with crural reinforcement with absorbable mesh (statistically significant, P = 0.017). Suture cruroplasty alone appears to be inadequate for hiatal hernias measuring 1-5 cm with significant recurrence rate and failure of antireflux surgery. Crural reinforcement with absorbable mesh may reduce hiatal hernia recurrence rate in small hiatal hernias.

e15066Background: Aberrant methylation of CpG sites within promoter regions of cancer-related genes is an important epigenetic event in carcinogenesis. The frequency of methylation changes of diffe...

The objective of this research is to study the effectiveness of using a stereoscopic visualization system for performing remote surgery. The use of stereoscopic vision has become common with the advent of the da Vinci® system (Intuitive, Sunnyvale CA). This system creates a virtual environment that consists of a 3-D display for visual feedback and haptic tactile feedback, together providing an intuitive environment for remote surgical applications. This study will use simple in vivo robotic surgical devices and compare the performance of surgeons using the stereoscopic interfacing system to the performance of surgeons using one dimensional monitors. The stereoscopic viewing system consists of two cameras, two monitors, and four mirrors. The cameras are mounted to a multi-functional miniature in vivo robot; and mimic the depth perception of the actual human eyes. This is done by placing the cameras at a calculated angle and distance apart. Live video streams from the left and right cameras are displayed on the left and right monitors, respectively. A system of angled mirrors allows the left and right eyes to see the video stream from the left and right monitor, respectively, creating the illusion of depth. The haptic interface consists of two PHANTOM Omni® (SensAble, Woburn Ma) controllers. These controllers measure the position and orientation of a pen-like end effector with three degrees of freedom. As the surgeon uses this interface, they see a 3-D image and feel force feedback for collision and workspace limits. The stereoscopic viewing system has been used in several surgical training tests and shows a potential improvement in depth perception and 3-D vision. The haptic system accurately gives force feedback that aids in surgery. Both have been used in non-survival animal surgeries, and have successfully been used in suturing and gallbladder removal. Bench top experiments using the interfacing system have also been conducted. A group of participants completed two different surgical training tasks using both a two dimensional visual system and the stereoscopic visual system. Results suggest that the stereoscopic visual system decreased the amount of time taken to complete the tasks. All participants also reported that the stereoscopic system was easier to utilize than the two dimensional system. Haptic controllers combined with stereoscopic vision provides for a more intuitive virtual environment. This system provides the surgeon with 3-D vision, depth perception, and the ability to receive feedback through forces applied in the haptic controller while performing surgery. These capabilities potentially enable the performance of more complex surgeries with a higher level of precision.

The purpose of this study was to investigate consistency of performance of robot-assisted surgical tasks in a virtual reality environment. Eight subjects performed two surgical tasks, bimanual carrying and needle passing, with both the da Vinci surgical robot and a virtual reality equivalent environment. Nonlinear analysis was utilized to evaluate consistency of performance by calculating the regularity and the amount of divergence in the movement trajectories of the surgical instrument tips. Our results revealed that movement patterns for both training tasks were statistically similar between the two environments. Consistency of performance as measured by nonlinear analysis could be an appropriate methodology to evaluate the complexity of the training tasks between actual and virtual environments and assist in developing better surgical training programs.

The purpose of this study was to use a simulated virtual reality environment for training of surgical skills and then to identify if the learning that occurred was transferable to a real world surgical task. The virtual surgical tasks consisted of bimanual carrying, needle passing and mesh alignment. In this ongoing study, the experimental group (n = 5) was trained by performing four blocks of the virtual surgical tasks using the da Vinci surgical robot. Pre and post training, all subjects were tested by performing a suturing task on a "life-like" suture pad. The control group (n = 5) performed only the suturing task. Significantly larger pre and post differences were revealed in time to task completion (p0.05) and total distance travelled by the dominant side instrument tip (p0.01) in the experimental group as compared to the control group. These differences were specific to the suture running aspect of the surgical task. In conclusion, virtual reality surgical skills training may produce a significant learning effect that can transfer to actual robot-assisted laparoscopic procedures.

The purpose of this study was to validate a complex robotic surgical task, mesh alignment, in virtual reality. Nine subjects unrolled and aligned a mesh onto an inanimate template for the mesh alignment task in both an actual (the da Vinci Robotic Surgical System) and a virtual environment. Data analysis included time to task completion, distance traveled, and speed, of the surgical instrument, as well as electromyography of the extensors and flexors of the dominant arm of the subject. Paired t-tests were used to compare the dependent variables between the actual and virtual environments. The virtual mesh alignment task was statistically similar for all variables except the flexor activity as compared to the actual task. In conclusion, virtual reality could be used as an effective environment to train the next generation of robot-assisted laparoscopic surgeons.

This article addresses emergent endoluminal technologies currently available for the treatment of gastroesophageal reflux disease (GERD) and compares it to the laparoscopic Nissen fundoplication. To date the mainstay of GERD therapy has been achieved with either open or laparoscopic fundoplication or life-long medical treatment. Endoluminal treatment modalities attempt to augment the gastroesophageal junction (GEJ) function by various techniques. We searched the Medline database from 1980 to 2004 for studies on endoscopic GERD techniques and laparoscopic fundoplications. Product investigators were contacted for data presented in abstract form only. Endoluminal management of GERD include using radiofrequency energy, injection of biocompatible polymers and endoluminal sutures to alter the GEJ and reduce reflux. Early results while encouraging, should be evaluated thoroughly and with caution before widespread use can be advocated. Endoscopic treatment of GERD has future promise, however, more experience and perhaps further refinement in techniques and technology must occur before widespread clinical application can be encouraged.