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Treball presentat a la Facultat de Veterinària de la Universitat Autònoma de Barcelona.Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen : a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from antiretroviral therapy-suppressed human immunodeficiency virus-infected individuals

Background: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Methods: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. Results: There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4(+) T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. Conclusions: The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4(+) T cells

Distinct effects of climate warming on populations of silver fir (Abies alba) across Europe

Aim Climate change is expected to modify growth trends of forests around the world. However, this modification may vary in strength and intensity across a species' biogeographical range. Here, we study European populations of silver fir (Abies alba) across its southern distribution limits in Spain, Italy and Romania. We hypothesized that growth trends of silver fir will differ across its distribution range, with a marked decline in growth in drought-prone regions near the species' southernmost biogeographical limits. Location Europe (Spain, Italy, Romania). Methods We collected tree-ring data from at least 1300 silver fir trees located in 111 sites. The dataset was used to assess and model growth trends, quantified as changes in basal area increment, and to determine how growth responds to climate. Results We found contrasting patterns of basal area increments among countries and sites. Populations of silver fir located outside the Mediterranean area (e.g. northern Italy, Romania) have shown a clear increase in growth over the last two decades, whereas most populations in Spain and southern Italy have displayed a marked decline in growth since the 1980s. The growth of silver fir forests at the south-western distribution limit is severely constrained by low spring-summer water availability, whereas growth of silver fir forests in non-Mediterranean areas is limited by cold conditions in late winter to early spring. Main conclusions Climate warming is distinctly modifying growth patterns and responses to climate in silver fir across most of the species' European distribution area. In south-western Europe the reduction in growth of many populations is related to an observed increase in aridity, whereas in more temperate areas warming is enhancing growth. Our results confirm a decline in the growth of silver fir at its south-western distribution limits as a consequence of climate warming

Col·leccions singulars a les biblioteques de la Universitat Autònoma de Barcelona

Les biblioteques de la Universitat Autònoma de Barcelona són, com la mateixa institució, entitats amb una història curta; però, malgrat que van començar la seva activitat fa menys de cinquanta anys, els seus fons han assolit una importància considerable i superen en quantitat els de moltes universitats centenàries del nostre context. Les col·leccions de fons antics de les biblioteques de la UAB són, per aquesta mateixa raó, limitades, si bé se n'han anat creant algunes d'especialitzades d'importància i valor singulars. Aquest llibre pretén donar-les a conèixer al món universitari, però també al públic en general. Moltes són col·leccions úniques, fruit del treball persistent del personal bibliotecari, del professorat i de la generositat de moltes persones particulars, que han donat o llegat a la nostra universitat els seus arxius, les seves biblioteques personals o les seves col·leccions especialitzades. Aquestes col·leccions comprenen molts àmbits de les ciències i de les humanitats i, molt sovint, es tracta de col·leccions úniques al nostre país. Hi trobareu també un ampli ventall de tipologies documentals en llengües diverses, des dels mapes fins als audiovisuals, des de les revistes i diaris fins als cartells, des dels fons antics fins als més actuals, arxius personals i fons institucionals. Les biblioteques de la Universitat, a més d'inventariar i catalogar aquests fons documentals, també porten a terme una tasca constant de preservació i difusió, que sovint inclou la digitalització dels documents, que després es posen a l'abast del públic general mitjançant el dipòsit digital institucional (ddd.uab.cat)

Guia d'actuació en pacients fumadors ingressats en unitats de salut mental

Fumadors; Pacients ingressats; Malalts mentalsSmoking; Patient admitted; Mental patientFumadores; Pacientes ingresados; Enfermo mentalAquesta guia pretén definir l'actuació de l'equip multidisciplinari que atén els pacients fumadors ingressats en unitats de salut mental

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one&nbsp;kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Switching From a Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen : A Randomized Clinical Trial to Determine the Effect on Peripheral Blood and Ileum Biopsies From Antiretroviral Therapy-suppressed Human Immunodeficiency Virus-infected Individuals

Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4 + T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4 + T cells. EudraCT 2014-004331-39. INDOOR evaluated the effect of switching from boosted protease inhibitor- to dolutegravir-based antiretroviral therapy on the HIV reservoir in peripheral blood and ileum. Residual plasma viremia and soluble CD14 levels decreased, but low-level HIV replication, the HIV reservoir, and immune activation remained unaffected

Guia per a la implementació territorial de projectes de millora en l’atenció a la complexitat

Pacients crònics complexos; Atenció a la cronicitat avançada; Ruta assistencial de la complexitatPacientes crónicos complejos; Atención a la cronicidad avanzada; Ruta asistencial de la complejidadComplex chronic patients; Attention to advanced chronicity; Complexity care routeEls objectius d’aquesta guia són: definir les característiques, les estratègies d’identificació i el model genèric d’atenció de PCC i MACA i aportar una visió pragmàtica de la implementació d’iniciatives de base territorial per a l’atenció d’aquests pacients

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics