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1.
Cell ; 176(1-2): 127-143.e24, 2019 01 10.
Article in English | MEDLINE | ID: mdl-30633903

ABSTRACT

DNA damage provokes mutations and cancer and results from external carcinogens or endogenous cellular processes. However, the intrinsic instigators of endogenous DNA damage are poorly understood. Here, we identify proteins that promote endogenous DNA damage when overproduced: the DNA "damage-up" proteins (DDPs). We discover a large network of DDPs in Escherichia coli and deconvolute them into six function clusters, demonstrating DDP mechanisms in three: reactive oxygen increase by transmembrane transporters, chromosome loss by replisome binding, and replication stalling by transcription factors. Their 284 human homologs are over-represented among known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis. Half of the tested human homologs promote DNA damage and mutation when overproduced in human cells, with DNA damage-elevating mechanisms like those in E. coli. Our work identifies networks of DDPs that provoke endogenous DNA damage and may reveal DNA damage-associated functions of many human known and newly implicated cancer-promoting proteins.


Subject(s)
DNA Damage/genetics , DNA Damage/physiology , DNA Repair/physiology , Bacterial Proteins/metabolism , Chromosomal Instability/physiology , DNA Replication/physiology , DNA-Binding Proteins/metabolism , Escherichia coli/metabolism , Genomic Instability , Humans , Membrane Transport Proteins/physiology , Mutagenesis , Mutation , Transcription Factors/metabolism
2.
J Med Virol ; 96(3): e29499, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38469919

ABSTRACT

Respiratory syncytial virus is associated with lower respiratory tract infections. As several types and genotypes can circulate at the same time, genomic characterization is important for timely epidemiological control and treatment measures. In the last 6 seasons (2017-2023), 191 236 nasopharyngeal swabs were processed for respiratory viruses to determine the etiology of acute respiratory infections, describe the incidence and distribution of RSV types and enrich the data of epidemiological molecular studies on RSV in Spain. The incidence of RSV reached 7% in the pre-pandemic season. RSV was most frequent in children under 5 years of age (12.6%), but was also significant in those over 70 years of age (5.63%). The measures taken to control SARS-CoV-2 infection were useful for RSV control and the incidence decreased to 1.8%, but caused a change in the types. Pre-pandemic, the majority circulating types were RSV-B/RSV-B/RSV-A and in the pandemic it was RSV-B/RSV-B. In the last season, RSV-B and RSV-A were detected in the same proportion. Genetic characterization showed three new clades. This has been taken into account to understand the epidemiology as well as the development of therapeutic and preventive strategies.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Child , Humans , Infant , Child, Preschool , Aged , Aged, 80 and over , Seasons , SARS-CoV-2/genetics , Respiratory Syncytial Virus Infections/epidemiology , Spain/epidemiology , Incidence , Pandemics , COVID-19/epidemiology , Respiratory Syncytial Virus, Human/genetics
3.
Brain Behav Immun ; 123: 28-42, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39243986

ABSTRACT

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, with a highly diverse genetic hereditary component, including altered neuronal circuits, that has an impact on communication skills and behaviours of the affected individuals. Beside the recognised role of neuronal alterations, perturbations of microglia and the associated neuroinflammatory processes have emerged as credible contributors to aetiology and physiopathology of ASD. Mutations in NRXN1, a member of the neurexin family of cell-surface receptors that bind neuroligin, have been associated to ASD. NRXN1 is known to be expressed by neurons where it facilitates synaptic contacts, but it has also been identified in glial cells including microglia. Asserting the impact of ASD-related genes on neuronal versus microglia functions has been challenging. Here, we present an ASD subject-derived induced pluripotent stem cells (iPSC)-based in vitro system to characterise the effects of the ASD-associated NRXN1 gene deletion on neurons and microglia, as well as on the ability of microglia to support neuronal circuit formation and function. Using this approach, we demonstrated that NRXN1 deletion, impacting on the expression of the alpha isoform (NRXN1α), in microglia leads to microglial alterations and release of IL6, a pro-inflammatory interleukin associated with ASD. Moreover, microglia bearing the NRXN1α-deletion, lost the ability to support the formation of functional neuronal networks. The use of recombinant IL6 protein on control microglia-neuron co-cultures or neutralizing antibody to IL6 on their NRXN1α-deficient counterparts, supported a direct contribution of IL6 to the observed neuronal phenotype. Altogether, our data suggest that, in addition to neurons, microglia are also negatively affected by NRXN1α-deletion, and this significantly contributes to the observed neuronal circuit aberrations.

4.
JAMA ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382234

ABSTRACT

Importance: Cardiac surgery-associated acute kidney injury (CSA-AKI) remains a significant problem following cardiopulmonary bypass (CPB). Various strategies are proposed to attenuate CSA-AKI, including extracorporeal blood purification (EBP), but little is known about the effect of EBP through an acrylonitrile-sodium methallylsulfonate/polyethyleneimine membrane during CPB. Objective: To determine whether the use of an EBP device in a nonemergent cardiac surgery population reduces CSA-AKI after CPB. Design, Setting, and Participants: This double-blind, randomized clinical trial was conducted in 2 tertiary hospitals in Spain. Patients 18 years or older undergoing nonemergent cardiac surgery who were at high risk for CSA-AKI were enrolled from June 15, 2016, through November 5, 2021, with follow-up data through February 5, 2022. Of 1156 patients assessed, 343 patients were randomized (1:1) to either receive EBP or standard care. Intervention: Nonselective EBP device connected to the CPB circuit. Main Outcomes and Measures: The primary outcome was the rate of CSA-AKI in the 7 days after randomization. Results: Among 343 patients randomized (169 to receive EBP and 174 to receive usual care), the mean (SD) age was 69 (9) years and 119 were females. The rate of CSA-AKI was 28.4% (95% CI, 21.7%-35.8%) in the EBP group vs 39.7% (95% CI, 32.3%-47.3%) in the standard care group (P = .03), with an adjusted difference of 10.4% (95% CI, 2.3%-18.5%) using a log-binomial model (P = .01). No significant differences (P > .05) were observed in most of the predefined clinical secondary end points or post hoc exploratory end points. In a sensitivity analysis, EBP was found to be more effective in terms of CSA-AKI reduction in patients with chronic kidney disease, diabetes, hypertension, low left ventricular ejection fraction (<40%), and lower body mass index (<30). No differences were observed between the groups in adverse events tracking. Conclusions and Relevance: The use of a nonselective EBP device connected to the CPB circuit in a nonemergent population of patients undergoing cardiac surgery was associated with a significant reduction of CSA-AKI in the first 7 days after surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02518087.

5.
BMC Nurs ; 23(1): 38, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38212761

ABSTRACT

BACKGROUND: Euthanasia has been incorporated into the health services of seven countries. The legalisation of these practices has important repercussions for the competences of nurses, and it raises questions about their role. When a patient with advanced disease expresses a wish to die, what is expected of nurses? What are the needs of these patients, and what kind of care plan do they require? What level of autonomy might nurses have when caring for these patients? The degree of autonomy that nurses might or should have when it comes to addressing such a wish and caring for these patients has yet to be defined. Recognising the wish to die as a nursing diagnosis would be an important step towards ensuring that these patients receive adequate nursing care. This study-protocol aims to define and validate the nursing diagnosis wish to die in patients with advanced disease, establishing its defining characteristics and related factors; to define nursing-specific interventions for this new diagnosis. METHODS: A prospective three-phase study will be carried out. Phase-A) Foundational knowledge: an umbrella review of systematic reviews will be conducted; Phase-B) Definition and validation of the diagnostic nomenclature, defining characteristics and related factors by means of an expert panel, a Delphi study and application of Fehring's diagnostic content validation model; Phase-C) Definition of nursing-specific interventions for the new diagnosis. At least 200 academic and clinical nurses with expertise in the field of palliative care or primary health care will be recruited as participants across the three phases. DISCUSSION: The definition of the wish to die as a nursing diagnosis would promote greater recognition and autonomy for nurses in the care of patients who express such a wish, providing an opportunity to alleviate underlying suffering through nursing-specific interventions and drawing attention to the needs of patients with advanced disease. The new diagnosis would be an addition to nursing science and would provide a framework for providing care to people with advanced disease who express such a wish. Nurses would gain professional autonomy about identifying, exploring and responding clinically to such a wish.

6.
Brain Behav Immun ; 112: 206-219, 2023 08.
Article in English | MEDLINE | ID: mdl-37327833

ABSTRACT

Adult hippocampal neurogenesis (AHN) is a process involved in numerous neurodegenerative diseases. Many researchers have described microglia as a key component in regulating the formation and migration of new neurons along the rostral migratory stream. Caspase-3 is a cysteine-aspartate-protease classically considered as one of the main effector caspases in the cell death program process. In addition to this classical function, we have identified the role of this protein as a modulator of microglial function; however, its action on neurogenic processes is unknown. The aim of the present study is to identify the role of Caspase-3 in neurogenesis-related microglial functions. To address this study, Caspase-3 conditional knockout mice in the microglia cell line were used. Using this tool, we wanted to elucidate the role of this protein in microglial function in the hippocampus, the main region in which adult neurogenesis takes place. After the reduction of Caspase-3 in microglia, mutant mice showed a reduction of microglia in the hippocampus, especially in the dentate gyrus region, a region inherently associated to neurogenesis. In addition, we found a reduction in doublecortin-positive neurons in conditional Caspase-3 knockout mice, which corresponds to a reduction in neurogenic neurons. Furthermore, using high-resolution image analysis, we also observed a reduction in the phagocytic capacity of microglia lacking Caspase-3. Behavioral analysis using object recognition and Y-maze tests showed altered memory and learning in the absence of Caspase-3. Finally, we identified specific microglia located specifically in neurogenic niche positive for Galectin 3 which colocalized with Cleaved-Caspase-3 in control mice. Taken together, these results showed the essential role of Caspase-3 in microglial function and highlight the relevant role of this specific microglial phenotype in the maintenance of AHN in the hippocampus.


Subject(s)
Caspase 3 , Hippocampus , Microglia , Animals , Mice , Caspase 3/metabolism , Hippocampus/metabolism , Mice, Knockout , Microglia/metabolism , Neurogenesis/physiology
7.
Proc Natl Acad Sci U S A ; 117(24): 13699-13707, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32467158

ABSTRACT

Adenovirus minor coat protein VI contains a membrane-disrupting peptide that is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high-resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and noninfectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wild-type (Ad5-wt) particles. Cryoelectron microscopy difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.


Subject(s)
Adenoviruses, Human/metabolism , Nucleocapsid Proteins/metabolism , Virus Assembly , Virus Internalization , Adenoviruses, Human/genetics , Adenoviruses, Human/ultrastructure , Cryoelectron Microscopy , Humans , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/genetics , Protein Binding , Protein Domains
8.
Rev Panam Salud Publica ; 47: e147, 2023.
Article in Spanish | MEDLINE | ID: mdl-37881799

ABSTRACT

This article presents the experience of the health policy dialogue on nursing held in Uruguay in 2021, based on the theory of change. Four working groups were held, with the participation of 725 people. The points discussed included: the shortage of registered nurses to implement programs and cover functions at all levels of health care; the poor visibility of the healthcare impact of the activities carried out; insufficient financial resources for undergraduate and postgraduate training; and poor integration of nurses in management teams and policy decision-making spaces in the country. Participants expressed the need to implement the national nursing development plan so that the country can: reduce the shortage of professionals; invest in job creation to meet the demand for professional care; improve staffing of services at all levels of care; improve working conditions; create new spaces for nurses by expanding their role through postgraduate training, while continuously improving the quality of training. Participants emphasized the need to increase intersectoral coordination in the areas of governance, regulation, and management, and to step up efforts to increase investment in health professionals in Uruguay.


Este artigo apresenta a experiência do diálogo político-sanitário sobre enfermagem realizado no Uruguai em 2021 com base na teoria da mudança. Foram organizados quatro grupos de trabalho, dos quais participaram 725 pessoas. Entre os pontos discutidos, destacam-se: a falta de profissionais graduados em enfermagem para desenvolver programas e cobrir funções em todos os níveis de atenção à saúde; a falta de visibilidade do impacto assistencial das atividades desenvolvidas; a insuficiência de recursos financeiros para programas de graduação e pós-graduação; e a pouca integração desses profissionais às equipes de gestão e aos espaços de tomada de decisão política no país. Os participantes indicaram a necessidade de implementar o plano nacional de desenvolvimento da enfermagem para que o país reduza o déficit de profissionais; invista na criação de cargos para atender à demanda por cuidados profissionais; melhore a dotação de pessoal nos serviços em todos os níveis de atenção; melhore as condições de trabalho; crie novas oportunidades de inserção para profissionais de enfermagem, ampliando suas funções por meio da pós-graduação; e aprimore continuamente a qualidade da formação. Os participantes enfatizaram a necessidade de aumentar a coordenação intersetorial nos aspectos de governança, regulação e gestão, bem como de acelerar os esforços no sentido de aumentar o investimento em profissionais de saúde no Uruguai.

9.
Genes Dev ; 29(2): 197-211, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25593309

ABSTRACT

How chromatin shapes pathways that promote genome-epigenome integrity in response to DNA damage is an issue of crucial importance. We report that human bromodomain (BRD)-containing proteins, the primary "readers" of acetylated chromatin, are vital for the DNA damage response (DDR). We discovered that more than one-third of all human BRD proteins change localization in response to DNA damage. We identified ZMYND8 (zinc finger and MYND [myeloid, Nervy, and DEAF-1] domain containing 8) as a novel DDR factor that recruits the nucleosome remodeling and histone deacetylation (NuRD) complex to damaged chromatin. Our data define a transcription-associated DDR pathway mediated by ZMYND8 and the NuRD complex that targets DNA damage, including when it occurs within transcriptionally active chromatin, to repress transcription and promote repair by homologous recombination. Thus, our data identify human BRD proteins as key chromatin modulators of the DDR and provide novel insights into how DNA damage within actively transcribed regions requires chromatin-binding proteins to orchestrate the appropriate response in concordance with the damage-associated chromatin context.


Subject(s)
Chromatin/metabolism , DNA Damage , Homologous Recombination/genetics , Receptors, Cell Surface/metabolism , Autoantigens/metabolism , Cell Line, Tumor , Gene Expression Regulation , Gene Silencing , Humans , Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism , Protein Binding , Protein Transport/genetics , Receptors for Activated C Kinase , Receptors, Cell Surface/genetics , Tumor Suppressor Proteins
10.
Int J Nurs Pract ; 29(6): e13157, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37127403

ABSTRACT

OBJECTIVE: To explore the experiences and emotions of individuals with depression and physical comorbidity within the context of psychoeducational group interventions led by primary care nurses in Catalunya (Spain). METHOD: A psychoeducational group intervention was conducted in the first semester of 2019 with 13 primary care teams (rural/urban) and 95 participants with depression and physical comorbidity. The qualitative research and phenomenological perspective were based on 13 field diaries and 7 semi-structured interviews carried out with the observer nurses. The interviews were recorded and transcribed. Codes were identified by segmenting the text into citations/verbatim accounts and emerging categories/subcategories by regrouping the codes. The results were triangulated among the researchers to identify and compare similarities and differences. RESULTS: Four major themes were found: (a) gender differences; (b) coping strategies and changes observed during the intervention; (c) functions of the group as a therapeutic element; and (d) the nurses' perceptions of the group experience. Gender differences were identified in relation to experiences and emotions. CONCLUSIONS: As some patients acquired skills/behaviours during the intervention that helped them initiate changes and the nurses were satisfied with the intervention, it is important to include this information when planning effective interventions for patients with this profile.


Subject(s)
Depression , Emotions , Humans , Depression/therapy , Comorbidity , Qualitative Research , Primary Health Care/methods
11.
BMC Pediatr ; 22(1): 488, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35971102

ABSTRACT

BACKGROUND: Difficulty in interpreting white blood cell (WBC) counts in cerebrospinal fluid (CSF) complicates the diagnosis of neonatal meningitis in traumatic lumbar punctures (LP). The aim of our study was to determine the correction factor for WBC counts in traumatic LP that offers the greatest diagnostic efficacy in meningitis. METHODS: We conducted a retrospective observational study of LP in neonates between January 2014 and December 2020. Traumatic LP was defined as a red blood cell (RBC) count ≥ 1,000 cells/mm3 CSF and pleocytosis as WBCs ≥ 20 cells/mm3 CSF. The CSF RBC:WBC ratio was analyzed by linear regression to determine a new correction factor. Cell count adjustments were also studied using the 500:1, the 1,000:1 ratio method, and the peripheral blood RBC:WBC ratio, using ROC curves and studies of accuracy (sensitivity and specificity). RESULTS: Overall, 41.0% of the 1,053 LPs included in the study were traumatic. The best results for effective WBC correction were the method based on the peripheral blood ratio (sensitivity = 1.0 and specificity = 0.9 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.9 for viral meningitis) and the 400:1 ratio (sensitivity = 1.0 and specificity = 0.8 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.8 for viral meningitis) obtained from linear regression (95% CI 381.7-427.4; R2 = 0.7). CONCLUSION: Both the peripheral blood correction and the 400:1 correction reduce the number of neonates classified with pleocytosis who were not eventually diagnosed with meningitis. Both methods might be a useful tool to clarify the neonatal meningitis diagnosis, offering neonatologists the possibility to assess the WBC count in traumatic LP.


Subject(s)
Meningitis, Bacterial , Meningitis, Viral , Humans , Infant, Newborn , Leukocyte Count , Leukocytosis/cerebrospinal fluid , Leukocytosis/diagnosis , Leukocytosis/etiology , Meningitis, Bacterial/microbiology , Retrospective Studies , Spinal Puncture
12.
Nucleic Acids Res ; 47(17): 9231-9242, 2019 09 26.
Article in English | MEDLINE | ID: mdl-31396624

ABSTRACT

Some viruses package dsDNA together with large amounts of positively charged proteins, thought to help condense the genome inside the capsid with no evidence. Further, this role is not clear because these viruses have typically lower packing fractions than viruses encapsidating naked dsDNA. In addition, it has recently been shown that the major adenovirus condensing protein (polypeptide VII) is dispensable for genome encapsidation. Here, we study the morphology and mechanics of adenovirus particles with (Ad5-wt) and without (Ad5-VII-) protein VII. Ad5-VII- particles are stiffer than Ad5-wt, but DNA-counterions revert this difference, indicating that VII screens repulsive DNA-DNA interactions. Consequently, its absence results in increased internal pressure. The core is slightly more ordered in the absence of VII and diffuses faster out of Ad5-VII- than Ad5-wt fractured particles. In Ad5-wt unpacked cores, dsDNA associates in bundles interspersed with VII-DNA clusters. These results indicate that protein VII condenses the adenovirus genome by combining direct clustering and promotion of bridging by other core proteins. This condensation modulates the virion internal pressure and DNA release from disrupted particles, which could be crucial to keep the genome protected inside the semi-disrupted capsid while traveling to the nuclear pore.


Subject(s)
Adenoviridae/genetics , Capsid Proteins/genetics , DNA, Viral/genetics , Viral Core Proteins/genetics , Genome, Viral/genetics , Humans , Viral Proteins/genetics , Virion/genetics , Virus Assembly
13.
Transpl Infect Dis ; 21(4): e13097, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31002443

ABSTRACT

Endotipsitis is a rare but severe complication of transjugular intrahepatic portosystemic shunt (TIPS), a device widely used to treat portal hypertension in adults, but sparsely used in children. We report a case of endotipsitis in a 3-year-old child affected of biliary atresia. She underwent a Kasai procedure at 3 months of age but, although the bile flow was restored, she presented upper gastrointestinal bleeding due to portal hypertension 1.5 years later. A TIPS was placed in order to control the hemorrhage. A year after TIPS placement, she started presenting repeated episodes of cholangitis. Blood cultures were positive to Enterobacter cloacae. Even with long antibiotic courses, adjusted to blood cultures, infectious signs were observed after antibiotic withdrawal. Device infection was demonstrated through Positron emission tomography-Computed tomography scan. The patient was listed for liver transplantation, and intravenous antibiotic treatment was maintained until stent removal during the liver transplant 8 months later. No infectious complications were demonstrated after the surgery. To the best of our knowledge, this is the first case report of endotipsitis described in a pediatric patient.


Subject(s)
Cholangitis/microbiology , Liver Transplantation , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Anti-Bacterial Agents/therapeutic use , Biliary Atresia/complications , Child, Preschool , Cholangitis/diagnosis , Cholangitis/drug therapy , Enterobacter cloacae/drug effects , Enterobacteriaceae Infections/drug therapy , Female , Gastrointestinal Hemorrhage/therapy , Humans
14.
Psychooncology ; 27(6): 1538-1544, 2018 06.
Article in English | MEDLINE | ID: mdl-29490118

ABSTRACT

INTRODUCTION: The Desire for Death Rating Scale (DDRS) and the short form of the Schedule of Attitudes toward Hastened Death (SAHD-5) are different approaches to assessing the wish to hasten death (WTHD). Both have clinical threshold scores for identifying individuals with a meaningfully elevated WTHD. However, the agreement between the 2 measures and patient opinions about assessment of the WTHD are unknown. OBJECTIVES: To compare the DDRS and SAHD-5 and to analyze patient opinions about assessment of the WTHD. METHODS: The WTHD was assessed in 107 patients with advanced cancer using both the DDRS and SAHD-5. Patients were subsequently asked their opinion about this assessment. RESULTS: Correlation between scores on the SAHD-5 and the DDRS was moderate, Spearman rho = 0.67 (P < .01). The SAHD-5 identified 13 patients (12.1%) at risk of the WTHD, and the DDRS identified 6 patients (5.6%) with a moderate-high WTHD (P > .05). Concordance between the DDRS and SAHD-5 in identifying individuals with an elevated WTHD was poor when using recommended cut-off scores, κ = 0.37 (P < 0.01) but could be improved by using different thresholds. Only 4 patients (3.8%) regarded the assessment questions as bothersome, and 90.6% considered it important that health-care professionals inquire about the WTHD. CONCLUSIONS: The SAHD-5 and DDRS appear to be appropriate methods for assessing the WTHD and could provide complementary information in clinical practice: the SAHD-5 to screen for risk of the WTHD and the DDRS as a clinical interview to explore it in greater detail. Assessment of the WTHD is well accepted by palliative care cancer patients.


Subject(s)
Neoplasms/psychology , Quality of Life/psychology , Surveys and Questionnaires/standards , Terminally Ill/psychology , Aged , Attitude to Death , Female , Humans , Male , Middle Aged , Palliative Care/psychology
15.
J Vasc Interv Radiol ; 29(6): 899-904, 2018 06.
Article in English | MEDLINE | ID: mdl-29798761

ABSTRACT

This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%).


Subject(s)
Cholestasis/therapy , Liver Transplantation , Postoperative Complications/therapy , Stents , Aged , Biocompatible Materials , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Treatment Outcome
16.
J Biol Phys ; 44(2): 225-235, 2018 06.
Article in English | MEDLINE | ID: mdl-29654426

ABSTRACT

We use the nano-dissection capabilities of atomic force microscopy to induce structural alterations on individual virus capsids in liquid milieu. We fracture the protein shells either with single nanoindentations or by increasing the tip-sample interaction force in amplitude modulation dynamic mode. The normal behavior is that these cracks persist in time. However, in very rare occasions they self-recuperate to retrieve apparently unaltered virus particles. In this work, we show the topographical evolution of three of these exceptional events occurring in T7 bacteriophage capsids. Our data show that single nanoindentation produces a local recoverable fracture that corresponds to the deepening of a capsomer. In contrast, imaging in dynamic mode induced cracks that separate the virus morphological subunits. In both cases, the breakage patterns follow intratrimeric loci.


Subject(s)
Bacteriophage T7/metabolism , Microscopy, Atomic Force , Bacteriophage T7/physiology , Biomechanical Phenomena , Capsid/chemistry , Capsid/metabolism , Time Factors , Virion/chemistry , Virion/metabolism
17.
Biochem Soc Trans ; 45(2): 499-511, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28408490

ABSTRACT

Microscopes are used to characterize small objects with the help of probes that interact with the specimen, such as photons and electrons in optical and electron microscopies, respectively. In atomic force microscopy (AFM), the probe is a nanometric tip located at the end of a microcantilever which palpates the specimen under study just as a blind person manages a walking stick. In this way, AFM allows obtaining nanometric resolution images of individual protein shells, such as viruses, in a liquid milieu. Beyond imaging, AFM also enables not only the manipulation of single protein cages, but also the characterization of every physicochemical property capable of inducing any measurable mechanical perturbation to the microcantilever that holds the tip. In the present revision, we start revising some recipes for adsorbing protein shells on surfaces. Then, we describe several AFM approaches to study individual protein cages, ranging from imaging to spectroscopic methodologies devoted to extracting physical information, such as mechanical and electrostatic properties. We also explain how a convenient combination of AFM and fluorescence methodologies entails monitoring genome release from individual viral shells during mechanical unpacking.


Subject(s)
Viral Proteins/metabolism , Viruses/ultrastructure , Adsorption , Biomechanical Phenomena , Genome, Viral , Microscopy, Atomic Force/methods , Viruses/genetics
18.
Phys Rev Lett ; 119(3): 038102, 2017 Jul 21.
Article in English | MEDLINE | ID: mdl-28777631

ABSTRACT

A virus binding to a surface causes stress of the virus cage near the contact area. Here, we investigate the potential role of substrate-induced structural perturbation in the mechanical response of virus particles to adsorption. This is particularly relevant to the broad category of viruses stabilized by weak noncovalent interactions. We utilize atomic force microscopy to measure height distributions of the brome mosaic virus upon adsorption from solution on atomically flat substrates and present a continuum model that captures our observations and provides estimates of elastic properties and of the interfacial energy of the virus, without recourse to indentation.


Subject(s)
Bromovirus , Microscopy, Atomic Force , Virion , Adsorption
20.
Palliat Med ; 31(6): 510-525, 2017 06.
Article in English | MEDLINE | ID: mdl-28124578

ABSTRACT

BACKGROUND: Patients with advanced conditions may present a wish to hasten death. Assessing this wish is complex due to the nature of the phenomenon and the difficulty of conceptualising it. AIM: To identify and analyse existing instruments for assessing the wish to hasten death and to rate their reported psychometric properties. DESIGN: Systematic review based on PRISMA guidelines. The COnsensus-based Standards for the selection of health Measurement INstruments checklist was used to evaluate the methodological quality of validation studies and the measurement properties of the instrument described. DATA SOURCES: The CINAHL, PsycINFO, Pubmed and Web of Science databases were searched from inception to November 2015. RESULTS: A total of 50 articles involving assessment of the wish to hasten death were included. Eight concerned instrument validation and were evaluated using COnsensus-based Standards for the selection of health Measurement INstruments criteria. They reported data for between two and seven measurement properties, with ratings between fair and excellent. Of the seven instruments identified, the Desire for Death Rating Scale or the Schedule of Attitudes toward Hastened Death feature in 48 of the 50 articles. The Schedule of Attitudes toward Hastened Death is the most widely used and is the instrument whose psychometric properties have been most often analysed. Versions of the Schedule of Attitudes toward Hastened Death are available in five languages other than the original English. CONCLUSION: This systematic review has analysed existing instruments for assessing the wish to hasten death. It has also explored the methodological quality of studies that have examined the measurement properties of these instruments and offers ratings of the reported properties. These results will be useful to clinicians and researchers with an interest in a phenomenon of considerable relevance to advanced patients.


Subject(s)
Attitude to Death , Euthanasia, Active, Voluntary , Psychometrics/instrumentation , Terminally Ill/psychology , Humans , Palliative Care
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