Вогнева підготовка курсантів ЗВО зі специфічними умовами навчання в умовах воєнного стану

У Національній поліції на діяльність праців­ників правоохоронних органів полягає велика від­повідальність, поліцейські мають бути максимально витриманними та обізнаними у своїй роботі, керува­тися виключно Конституцією України та українським законодавством, адже людське життя, честь та гід­ність є найбільшою цінністю у нашій державі. Для забезпечення правопорядку та захисту життя і здо­ров'я населення, правоохоронці проходять відповід­ну підготовку з вогневої, тактико-спеціальної та пси­хологічної підготовки. Знання з вогневої підготовки є дуже важливими, адже застосовуючи вогнепальну зброю, поліцейський повинен знати не тільки мате­ріальну частину зброї, техніку використання і її ма­теріальну частину, а і нормативно-правову базу, ке­руючись якою, правоохоронець може застосовувати зброю. Вогнева підготовка в поліції має підвищи­ти майстерність та міцність курсантів у стрільбі, збільшити їх уважність та пильність, підвищити рівень дисципліни. Якщо курсанти обладнані та­кими вміннями, вони зможуть впевнено викону­вати свої функції, так як зможуть вчасно реагу­вати на змінні ситуації та виконувати професійні обов'язки. Для того, щоб навчитися працювати з вогнепальною зброєю, курсанти повинні також виробляти вміння і навички виконання такти- ко-спеціальних дій, практикуючись у створенні оптимальних стрільбищах, визначенні точних дій під час перестрілок, виконанні рятувальних дій при надзвичайній ситуації та інше. Одним із найбільш важливих пріоритетів вог­невої підготовки курсантів є уміння обирати опти­мальні позиції для стрільби, аналізувати та оціню­вати місцевість, проводити стрільбу та приймати швидкі рішення. Курсанти повинні чітко розуміти, коли дозволений вогонь, які наслідки можуть виникнути та як повідомляти керівництву про ви­користання зброї. Хоча вогнева підготовка в На­ціональній поліції вимагає розгорнутого набору знань та вмінь, проте вона є надзвичайно важ­ливою, усвідомлюючи те, що кожний поліцейсь­кий ризикує своїм життям на службі задля захисту громади та її громадян. Добре підготовлений полі­цейський є ключем до успішної боротьби зі зло- чиннистю та збереження безпеки поліцейського та суспільтсва. Тож вогнева підготовка курсантів у поліції - це важливий елемент, що дозволяє га­рантувати безпеку мешканців міст та забезпечує добре опанування поліцейської вправи. Дисци­пліна з вогневої підготовки є основною в закла­дах вищої освіти зі специфічними умовами нав­чання. В роботі викладений матеріал щодо важ­ливості даного предмету в цілому та особливості такої підготовки в умовах воєнного стану

ATP Release from Dying Autophagic Cells and Their Phagocytosis Are Crucial for Inflammasome Activation in Macrophages

Pathogen-activated and damage-associated molecular patterns activate the inflammasome in macrophages. We report that mouse macrophages release IL-1β while co-incubated with pro-B (Ba/F3) cells dying, as a result of IL-3 withdrawal, by apoptosis with autophagy, but not when they are co-incubated with living, apoptotic, necrotic or necrostatin-1 treated cells. NALP3-deficient macrophages display reduced IL-1β secretion, which is also inhibited in macrophages deficient in caspase-1 or pre-treated with its inhibitor. This finding demonstrates that the inflammasome is activated during phagocytosis of dying autophagic cells. We show that activation of NALP3 depends on phagocytosis of dying cells, ATP release through pannexin-1 channels of dying autophagic cells, P2X7 purinergic receptor activation, and on consequent potassium efflux. Dying autophagic Ba/F3 cells injected intraperitoneally in mice recruit neutrophils and thereby induce acute inflammation. These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses

Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

<p>Abstract</p> <p>Objective</p> <p>To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).</p> <p>Case report</p> <p>Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate <it>PEX </it>genes revealed a homozygous c.865_866insA mutation in the <it>PEX2 </it>gene leading to a frameshift 17 codons upstream of the stop codon. <it>PEX </it>gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).</p> <p>Conclusions</p> <p>Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.</p

Increased Activity of Cell Surface Peptidases in HeLa Cells Undergoing UV-Induced Apoptosis Is Not Mediated by Caspase 3

We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage. All the agents except for DEVD had no effect on the level of caspase 3 activity in the cells. The results suggest that other caspases may cleave PARP in these cells. Both 3AB and DEVD treatment reduced the level of actin cleavage seen in the apoptotic cells. The increase in CSP activity observed in cells undergoing UVB-induced apoptosis appears to involve PARP but not caspase 3

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Objectives Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6). Materials and methods The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model. Results In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB). Conclusion CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction. The finding of HS-causing mutations in PEX1 and PEX6 shows that HS represents the mild end of the ZSSD spectrum, though these conditions were previously thought to be distinct nosological entities. Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants, and show the patterns of Pex1, Pex14 and Pex6 immunoreactivity in the mouse retina. While Ratbi et al. found more HS-causing mutations in PEX1 than in PEX6, as is the case for ZSSD, in this cohort PEX6 variants predominate, suggesting both genes play a significant role in HS. The PEX6 variant c.1802G>A, p.(R601Q), reported previously in compound heterozygous state in one HS and three ZSSD cases, was found in compound heterozygous state in three HS families. Haplotype analysis suggests a common founder variant. All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles. The clinical overlap of HS with the more common Usher syndrome and lack of peroxisomal abnormalities on plasma screening suggest that HS may be under-diagnosed. Recognition of AI is key to the accurate diagnosis of HS

Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death

Herpes Simplex Virus Type 1 Infection Facilitates Invasion of Staphylococcus aureus into the Nasal Mucosa and Nasal Polyp Tissue

Background: Staphylococcus aureus (S. aureus) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. However the mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue. Methodology/Principal Findings: Inferior turbinate and nasal polyp samples were cultured and infected with either HSV1 alone, S. aureus alone or a combination of both. Both in turbinate mucosa and nasal polyp tissue, HSV1, with or without S. aureus incubation, led to focal infection of outer epithelial cells within 48 h, and loss or damage of the epithelium and invasion of HSV1 into the lamina propria within 72 h. After pre-infection with HSV1 for 24 h or 48 h, S. aureus was able to pass the basement membrane and invade the mucosa. Epithelial damage scores were significantly higher for HSV1 and S. aureus co-infected explants compared with control explants or S. aureus only-infected explants, and significantly correlated with HSV1-invasion scores. The epithelial damage scores of nasal polyp tissues were significantly higher than those of inferior turbinate tissues upon HSV1 infection. Consequently, invasion scores of HSV1 of nasal polyp tissues were significantly higher than those of inferior turbinate mucosa in the HSV1 and co-infection groups, and invasion scores of S. aureus of nasal polyp tissues were significantly higher than those of inferior turbinate tissues in the co-infection group. Conclusions/Significance: HSV1 may lead to a significant damage of the nasal epithelium and consequently may facilitate invasion of S. aureus into the nasal mucosa. Nasal polyp tissue is more susceptible to the invasion of HSV1 and epithelial damage by HSV1 compared with inferior turbinate mucosa

Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress

Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy