Evaluation of the police operational tactical procedures for reducing officer injuries resulting from physical interventions in problematic arrests. The case of the Municipal Police of Cádiz (Spain)

Objectives: This paper describes some operational tactical procedures (OTP) and discusses the results of a 14-year-long study, spanning the period 2003-2016, conducted by the Municipal Police of Cadiz, Spain, which comprised 3 time periods: 2003-2006, when the officers were trained in traditional policing procedures; 2007-2013, when the officers were taught an innovative set of OTP in the form of a basic set of self-defense and arrest mechanisms, different from the traditional policing procedures that rely on martial arts and combat sports; and finally 2014-2016, when the OTP training was discontinued. The aim of this study was to improve policing and reduce officer injuries resulting from interventions in controversial or violent situations, such as problematic arrests. Material and Methods: The study involved 162 police officers and commanders of the Municipal Police of Cadiz, who were in street duty for their first time. There were 8 females and 154 males aged 24-55 years. Three OTP stages are shown as examples. Results: Based on the analysis of "training hours" and "physical interventions in problematic arrests," the results were: 1) the number of sick leaves in the police was identical according to the number of arrests, and 2) data on sick leaves show remarkable differences among the 3 periods under analysis. Conclusions: The OTP-based training substantially reduced officer sick leaves. The overall reduction in sick leaves in the period 2007-2013 was observed that cannot be ascribed to a decrease in criminal acts, and hence in police physical interventions

Safety of permanent pacemaker implantation: a prospective study

Although pacemaker implantation is considered to be low risk, it is not exempt from complications and technical failures during the procedure, both in the short and long term, and the complications that such patients may present remain unknown. The aim has been to analyze the complication rates associated with permanent pacing and to identify if these differ between patients with or without previous antithrombotic therapy. We used a prospective, single center, observational study of 310 adult patients with indications of permanent pacing. They were hospitalized from 1 January to 31 December 2014 and followed up for 6 months after the pacemaker implant. The participants were distributed into two groups according to the antithrombotic therapy prior to the implant. The most frequent major complications were pneumothorax (3.87%) and lead dislodgement (8.39%), while superficial phlebitis (12.90%) and uncomplicated hematomas (22.58%) were presented as the most recurrent minor complications. Hematomas were the most frequent minor complication in the antithrombotic therapy cohort, and shoulder pain was reported as the most recurrent minor complication in the non-exposed group. Finding out about complications in pacemaker implants enables a complete view of the process, and hence the prioritization of actions aimed at improving safety and reducing associated risks

Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence

Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life-extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR-125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1- dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease

Immunization strategies targeting newly arrived migrants in Non-EU countries of the mediterranean basin and black sea

Background: The World Health Organization recommends that host countries ensure appropriate vaccinations to refugees, asylum seekers and migrants. However, information on vaccination strategies targeting migrants in host countries is limited. Methods: In 2015-2016 we carried out a survey among national experts from governmental bodies of 15 non-EU countries of the Mediterranean and Black Sea in order to document and share national vaccination strategies targeting newly arrived migrants. Results: Four countries reported having regulations/procedures supporting the immunization of migrants at national level, one at sub-national level and three only targeting specific population groups. Eight countries offer migrant children all the vaccinations included in their national immunization schedule; three provide only selected vaccinations, mainly measles and polio vaccines. Ten and eight countries also offer selected vaccinations to adolescents and adults respectively. Eight countries provide vaccinations at the community level; seven give priority vaccines in holding centres or at entry sites. Data on administered vaccines are recorded in immunization registries in nine countries. Conclusions: Although differing among countries, indications for immunizing migrants are in place in most of them. However, we cannot infer from our findings whether those strategies are currently functioning and whether barriers to their implementation are being faced. Further studies focusing on these aspects are needed to develop concrete and targeted recommendations for action. Since migrants are moving across countries, development of on-line registries and cooperation between countries could allow keeping track of administered vaccines in order to appropriately plan immunization series and avoid unnecessary vaccinations

Rpd3l contributes to the DNA damage sensitivity of saccharomyces cerevisiae checkpoint mutants

DNA replication forks that are stalled by DNA damage activate an S-phase checkpoint that prevents irreversible fork arrest and cell death. The increased cell death caused by DNA damage in budding yeast cells lacking the Rad53 checkpoint protein kinase is partially suppressed by deletion of the EXO1 gene. Using a whole-genome sequencing approach, we identified two additional genes, RXT2 and RPH1, whose mutation can also partially suppress this DNA damage sensitivity. We provide evidence that RXT2 and RPH1 act in a common pathway, which is distinct from the EXO1 pathway. Analysis of additional mutants indicates that suppression works through the loss of the Rpd3L histone deacetylase complex. Our results suggest that the loss or absence of histone acetylation, perhaps at stalled forks, may contribute to cell death in the absence of a functional checkpoint.Cancer Research UK FC001066UK Medical Research Council FC001066Wellcome Trust FC001066European Molecular Biology Organization ALTF 263–2011European Research Council Advanced 669424-CHROMORE

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Cognitive reserve mediates the severity of certain neuropsychological deficits related to cocaine use disorder

Introduction: The concept of cognitive reserve (CR) is being considered in the field of substance use disorder (SUD) by observing that there are individuals whose brain alterations are not related to the cognitive symptomatology they present. Aims: Our aims were to characterise the possible neuropsychological deficits in a sample of subjects with SUD compared to a control group and to determine whether the degree of CR is a mediator in the cognitive functioning of these patients. Methods: To perform these objectives, the study involved a sample of subjects with SUD in outpatient treatment and a control group. A CR questionnaire and a comprehensive neuropsychological assessment were administered, and we also collected data related to drug consumption and psychological well-being. Results: The SUD group showed poorer performance compared to the control group in several cognitive domains (attention, declarative memory, executive functions and emotional perception), as well as in psychological comfort. Interestingly, we observed that the deficits found in attention, declarative memory and executive functions were mediated by the CR level of the participants, an effect that we did not observe in the rest of the variables registered. Conclusion: Our results suggest that long-term drug consumption leads to cognitive deficits and affects the psychological well-being of the subjects. Moreover, the CR should be taken into account during the assessment and rehabilitation of patients with SUD due to its protective role against certain neuropsychological deficits.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Role of vitamin A/retinoic acid in regulation of embryonic and adult hematopoiesis

Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with pegIFNα+ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against fve JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVRThis study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers PI14/01094 and PI17/00657 to JB, PI17/00903 to JGG, PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11-241). Te study was also funded by the RD16CIII/0002/0002, RD16/0025/0018, and RD16/0025/0017 projects as part of the Plan Nacional R+D+I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER

Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion

Genome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR