Publications by authors named "Victoria Garcia"

34 Publications

Higher levels of allograft injury in black patients early after heart transplantation.

J Heart Lung Transplant 2021 Dec 23. Epub 2021 Dec 23.

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laborarory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Department of Medicine, Stanford University School of Medicine, Palo Alto, California. Electronic address:

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.
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http://dx.doi.org/10.1016/j.healun.2021.12.006DOI Listing
December 2021

Integrating digital documents by means of concept maps: testing an intervention program with eye-movements modelling examples.

Heliyon 2021 Dec 16;7(12):e08607. Epub 2021 Dec 16.

University of Valencia, Spain.

When using the Internet to learn about a curricular topic students face the challenge of not only understanding each single document, but also of integrating the ideas in a combined representation. Several intervention studies have tested instructional methods, such as building concept maps, aimed at teaching integration of multiple documents to Secondary education and older students. However, building a concept map may be demanding for learners and requires competencies to build maps in an appropriate way. In the current study we explore the extent to which such integration processes relying a concept map mapping instruction can be efficiently taught to 6 grade students. Specifically, we tested a program which included eye-movement modeling examples (EMMEs) and self-explanation prompts on comprehension and concept mapping in a natural educational setting. An active control group received a similar instruction without EMMEs. Students were randomly assigned to the intervention ( = 34) or active control ( = 32) groups, and participated in 1-h sessions during four consecutive days. Results indicated that EMME group learnt better than the control group the phases to construct a concept map, as measured in a questionnaire. However, from pre to post test, the EMME group didn't improve comprehension as measured by open-ended reading comprehension questions or in a delayed summary. We conclude that EMMEs can be used to foster literacy strategy instruction of primary school students.
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http://dx.doi.org/10.1016/j.heliyon.2021.e08607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688559PMC
December 2021

Effect of ionizing radiation on human myeloperoxidase: Reaction with hydrated electrons.

J Photochem Photobiol B 2022 Jan 27;226:112369. Epub 2021 Nov 27.

Universidade da Coruña, Chemical Reactivity & Photoreactivity Group (REACT!), Department of Chemistry, CICA & Faculty of Sciences, A Zapateira s/n, E-15071 A Coruña, Spain. Electronic address:

Myeloperoxidase (MPO) is a myeloid-lineage restricted enzyme largely expressed in the azurophilic granules of neutrophils. It catalyses the formation of reactive oxygen species, mainly hypochlorous acid, contributing to anti-pathogenic defense. Disorders in the production or regulation of MPO may lead to a variety of health conditions, mainly of inflammatory origin, including autoimmune inflammation. We have studied the effect of ionizing radiation on the activity of MPO, as measured by the capacity retained by the enzyme to produce hypochlorous acid as reactive oxygen species after exposure to successive doses of solvated electrons, the strongest possible one-e reducing agent in water. Chlorination activity was still present after a very high irradiation dose, indicating that radiation damage does not take place at the active site, hindered in the core of MPO structure. Decay kinetics show a dependence on the wavelength, supporting that the process must occur at peripheral functional groups situated on external and readily accessible locations of the enzyme. These results are relevant to understand the mechanism of resistance of our innate anti-pathogenic defense system and also to get insight into potential strategies to regulate MPO levels as a therapeutic target in autoimmune diseases.
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http://dx.doi.org/10.1016/j.jphotobiol.2021.112369DOI Listing
January 2022

Making water smart.

Water Sci Technol 2020 12;82(12):v-vii

CALAGUA - Unidad Mixta UV-UPV, Departament d'Enginyeria Química, Universitat de València, Avinguda de la Universitat s/n, 46100, Burjassot, València, Spain, E-mail:

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http://dx.doi.org/10.2166/wst.2020.581DOI Listing
December 2020

[Deaths by COVID-19 in Spain and mortality statistics].

Gac Sanit 2021 May-Jun;35(3):303-304. Epub 2020 Sep 15.

Instituto de Medicina Legal y Ciencias Forenses de Palencia, Salamanca y Valladolid, Valladolid, España.

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http://dx.doi.org/10.1016/j.gaceta.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492060PMC
May 2021

Bronchiolitis obliterans syndrome-free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis.

J Heart Lung Transplant 2019 01 25;38(1):5-16. Epub 2018 Sep 25.

Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Divisions of General Medical Education, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Electronic address:

Background: Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist.

Methods: This retrospective cohort study of primary LTx recipients (1994-2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data.

Results: Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99-3.30 years) and 3.58 years (95% CI, 3.53-3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05).

Conclusions: Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.
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http://dx.doi.org/10.1016/j.healun.2018.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431291PMC
January 2019

Infection of novel reassortant H1N2 and H3N2 swine influenza A viruses in the guinea pig model.

Vet Res 2018 07 27;49(1):73. Epub 2018 Jul 27.

Departamento de Medicina Preventiva Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa, 11735, Santiago, Chile.

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) were identified in commercial farms in Chile. These viruses contained H1, H3 and N2 sequences, genetically divergent from IAVs described worldwide, associated with pandemic internal genes. Guinea pigs were used as human surrogate to evaluate the infection dynamics of these reassortant viruses, compared with a pandemic H1N1 virus. All viruses replicated and were shed in the upper respiratory tract without prior adaptation although H1N2 viruses showed the highest shedding titers. This could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.
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http://dx.doi.org/10.1186/s13567-018-0572-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062863PMC
July 2018

Long-term outcomes and transmission rates in hepatitis C virus-positive donor to hepatitis C virus-negative kidney transplant recipients: Analysis of United States national data.

Clin Transplant 2017 Oct 19;31(10). Epub 2017 Aug 19.

Section of Hepatology, Virginia Commonwealth University, Richmond, VA, USA.

The use of kidneys from hepatitis C virus (HCV)-positive (D+) deceased donors for HCV-negative recipients (R-) might increase the donor pool. We analyzed the national Organ Procurement and Transplant Network (OPTN) registry from 1994 to 2014 to compare the outcomes of HCV D+/R- (n = 421) to propensity-matched HCV-negative donor (D-)/R- kidney transplants, as well as with waitlisted patients who never received a transplant, in a 1:5 ratio (n = 2105, per matched group). Both 5-year graft survival (44% vs 66%; P < .001) and patient survival (57% vs 79%; P < .001) were inferior for D+/R- group compared to D-/R-. Nevertheless, 5-year patient survival from the time of wait listing was superior for D+/R- when compared to waitlisted controls (68% vs 43%; P < .001). Of the 126 D+/R- with available post-transplant HCV testing, HCV seroconversion was confirmed in 62 (49%), likely donor-derived. Five-year outcomes were similar between D+/R- that seroconverted vs D+/R- that did not (n = 64). Our analysis shows inferior outcomes for D+/R- patients although detailed data on pretransplant risk factors was not available. Limited data suggest that HCV transmission occurred in half of HCV D+/R- patients, although this might not have been the primary factor contributing to the poor observed outcomes.
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http://dx.doi.org/10.1111/ctr.13055DOI Listing
October 2017

Novel Avulaviruses in Penguins, Antarctica.

Emerg Infect Dis 2017 07;23(7):1212-1214

We identified 3 novel and distinct avulaviruses from Gentoo penguins sampled in Antarctica. We isolated these viruses and sequenced their complete genomes; serologic assays demonstrated that the viruses do not have cross-reactivity between them. Our findings suggest that these 3 new viruses represent members of 3 novel avulavirus species.
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http://dx.doi.org/10.3201/eid2307.170054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512496PMC
July 2017

Diagnosing the Decades-Long Rise in the Deceased Donor Kidney Discard Rate in the United States.

Transplantation 2017 03;101(3):575-587

1 United Network for Organ Sharing, Richmond, VA.

Background: The proportion of deceased donor kidneys recovered for transplant but discarded increased steadily in the United States over 2 decades, from 5.1% in 1988 to 19.2% by 2009. Over 100 000 patients are waiting for a kidney transplant, yet 3159 kidneys were discarded in 2015.

Methods: We evaluated trends in donor characteristics, discard reasons, and Organ Procurement Organization-specific discard rates. Multivariable regression and propensity analysis were used to estimate the proportion of the discard rate rise in the 2000s attributable to changes in donor factors and decisions to biopsy and pump kidneys.

Results: This study found that at least 80% of the discard rate rise can be explained by the recovery of kidneys from an expanding donor pool and changes in biopsy and pumping practices. However, a residual discard rate increase could not be explained by changes in these factors. From 1987 to 2009, median donor age rose from 26 to 43 years; median Kidney Donor Risk Index increased from 1.1 in 1994 to 1.3 in 2009. Our findings suggest that the increase from 10% to 30% in the proportion of kidneys pumped during the 2000s served as a buffer, keeping the discard rate from rising even higher than it did.

Conclusions: The majority of the kidney discard rate rise can be explained by the broadening donor pool. However, the presence of an unexplained, residual increase suggests behavioral factors (eg, increased risk aversion) and/or allocation inefficiencies may have played a role. Reducing risk aversion, improving allocation, and more often pumping less-than-ideal, yet potentially transplantable kidneys, may help reverse the trend.
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http://dx.doi.org/10.1097/TP.0000000000001539DOI Listing
March 2017

Health Concerns of Northeastern Pennsylvania Residents Living in an Unconventional Oil and Gas Development County.

Public Health Nurs 2016 11 14;33(6):502-510. Epub 2016 Apr 14.

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Objectives: This study was conducted to describe the health concerns of residents of an unconventional oil and natural gas development (UOGD) community and identify methods to best disseminate health information to the residents.

Design And Sample: A qualitative descriptive study of 27 residents of Wyoming County, Pennsylvania, was conducted.

Results: Residents described their health concerns in terms of their changing community as a result of UOGD, their feelings of stress and powerlessness related to these changes, and the limited response of their local policymakers and protective agencies. There were indications of misinformation related to routine environmental health and UOGD environmental risks. Web-based educational programs with downloadable printed materials to bridge the knowledge gaps of residents and health professionals are recommended.

Conclusions: Recommendations include public health nurses providing education to communities and other health professionals regarding environmental health risks, working with communities to advocate for health-protective regulations, and adopting a community-based participatory approach to meet the needs of community members.
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http://dx.doi.org/10.1111/phn.12265DOI Listing
November 2016

Effects of an Oral Nutritional Supplementation Plus Physical Exercise Intervention on the Physical Function, Nutritional Status, and Quality of Life in Frail Institutionalized Older Adults: The ACTIVNES Study.

J Am Med Dir Assoc 2015 May 2;16(5):439.e9-439.e16. Epub 2015 Apr 2.

Medical Affairs Department, Nestlé Health Science-Nestlé España, Barcelona, Spain.

Objectives: The objective of this study was to assess the effects of a hyperproteic, hypercaloric oral nutritional supplement with prebiotic fiber, vitamin D, and calcium, plus a standardized physical intervention, in the functional status, strength, nutritional status, and quality of life of frail institutionalized older adults.

Design: Multicentric prospective observational study under usual clinical practice conditions.

Setting: Four nursing homes from Burgos (2), Albacete, and Madrid, Spain.

Participants: Participants included 91 institutionalized older adults (age ≥70), able to walk 50 m, and meeting at least 3 of the Fried frailty phenotype criteria.

Intervention: Daily intake of two 200-mL bottles of an oral nutritional supplement, each bottle containing 300 kcal, 20 g protein, 3 g fiber, 500 IU vitamin D, and 480 mg calcium, plus a standardized physical exercise training consisting of flexibility, balance, and strengthening exercises for arms and legs, 5 days per week.

Measurements: Short Physical Performance Battery (SPPB), Short-Form-Late-Life Function and Disability Instrument (SF-LLFDI) function subscale, handgrip strength, EuroQoL-5 Dimensions visual analogic scale (EQ5DVAS), weight, body mass index (BMI), and Short-Form Mini Nutritional Assessment (MNA-SF) at baseline and 6 and 12 weeks.

Results: Forty-eight participants (52.7%) improved at least 1 point in the SPPB at week 6, and 44 (48.4%) did so at week 12; 39 participants (42.9%) improved at least 2 points in the SF-LLFDI at week 6, and 46 (50.5%) at week 12. Participants improved their quality of life measured with the EQ5DVAS by 6% (95% confidence interval [CI] 3%-10%) at week 6, and by 5% (95% CI 0%-10%) at week 12. They also improved their nutritional status (weight gain, BMI increase, and higher MNA-SF scores at 6- and 12-week follow-up). This improvement was higher in participants with more frailty criteria, lower functional level, lower vitamin D levels, and poorer nutritional status.

Conclusion: A 12-week intervention with oral nutritional supplementation plus physical exercise improves function, nutritional status, and quality of life in frail institutionalized older adults.
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http://dx.doi.org/10.1016/j.jamda.2015.02.005DOI Listing
May 2015

Distinct modes of antigen presentation promote the formation, differentiation, and activity of foxp3+ regulatory T cells in vivo.

J Immunol 2015 Apr 16;194(8):3784-97. Epub 2015 Mar 16.

The Wistar Institute, Philadelphia, PA 19104

How the formation and activity of CD4(+)Foxp3(+) regulatory T cells (Tregs) are shaped by TCR recognition of the diverse array of peptide:MHC complexes that can be generated from self-antigens and/or foreign Ags in vivo remains poorly understood. We show that a self-peptide with low (but not high) stimulatory potency promotes thymic Treg formation and can induce conventional CD4(+) T cells in the periphery to become Tregs that express different levels of the transcription factor Helios according to anatomical location. When Tregs generated in response to this self-peptide subsequently encountered the same peptide derived instead from influenza virus in the lung-draining lymph nodes of infected mice, they proliferated, acquired a T-bet(+)CXCR3(+) phenotype, and suppressed the antiviral effector T cell response in the lungs. However, these self-antigen-selected Tregs were unable to suppress the antiviral immune response based on recognition of the peptide as a self-antigen rather than a viral Ag. Notably, when expressed in a more immunostimulatory form, the self-peptide inhibited the formation of T-bet(+)CXCR3(+) Tregs in response to viral Ag, and Ag-expressing B cells from these mice induced Treg division without upregulation of CXCR3. These studies show that a weakly immunostimulatory self-peptide can induce thymic and peripheral Foxp3(+) Treg formation but is unable to activate self-antigen-selected Tregs to modulate an antiviral immune response. Moreover, a strongly immunostimulatory self-peptide expressed by B cells induced Tregs to proliferate without acquiring an effector phenotype that allows trafficking from the draining lymph node to the lungs and, thereby, prevented the Tregs from suppressing the antiviral immune response.
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http://dx.doi.org/10.4049/jimmunol.1402960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390510PMC
April 2015

Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men who have sex with men be recommended?

J Int AIDS Soc 2014 2;17(4 Suppl 3):19661. Epub 2014 Nov 2.

Infectious Diseases Unit, Hospital Virgen de la Victoria, Málaga, Spain.

Introduction: Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition (1). It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors.

Materials And Methods: Prospective study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern Spain) during October 2012-May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) (3).

Statistics Analysis: SPSS 17.0.

Results: 255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was 607 (440-824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co-infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2-7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use.

Conclusions: STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225393PMC
http://dx.doi.org/10.7448/IAS.17.4.19661DOI Listing
January 2016

The degree of CD4+ T cell autoreactivity determines cellular pathways underlying inflammatory arthritis.

J Immunol 2014 Apr 3;192(7):3043-56. Epub 2014 Mar 3.

The Wistar Institute, Philadelphia, PA 19104.

Although therapies targeting distinct cellular pathways (e.g., anticytokine versus anti-B cell therapy) have been found to be an effective strategy for at least some patients with inflammatory arthritis, the mechanisms that determine which pathways promote arthritis development are poorly understood. We have used a transgenic mouse model to examine how variations in the CD4(+) T cell response to a surrogate self-peptide can affect the cellular pathways that are required for arthritis development. CD4(+) T cells that are highly reactive with the self-peptide induce inflammatory arthritis that affects male and female mice equally. Arthritis develops by a B cell-independent mechanism, although it can be suppressed by an anti-TNF treatment, which prevented the accumulation of effector CD4(+) Th17 cells in the joints of treated mice. By contrast, arthritis develops with a significant female bias in the context of a more weakly autoreactive CD4(+) T cell response, and B cells play a prominent role in disease pathogenesis. In this setting of lower CD4(+) T cell autoreactivity, B cells promote the formation of autoreactive CD4(+) effector T cells (including Th17 cells), and IL-17 is required for arthritis development. These studies show that the degree of CD4(+) T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis.
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http://dx.doi.org/10.4049/jimmunol.1302528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974175PMC
April 2014

Viral antigen induces differentiation of Foxp3+ natural regulatory T cells in influenza virus-infected mice.

J Immunol 2013 Jun 10;190(12):6115-25. Epub 2013 May 10.

The Wistar Institute, Philadelphia, PA 19104, USA.

We examined the formation, participation, and functional specialization of virus-reactive Foxp3(+) regulatory T cells (Tregs) in a mouse model of influenza virus infection. "Natural" Tregs generated intrathymically, based on interactions with a self-peptide, proliferated in response to a homologous viral Ag in the lungs and, to a lesser extent, in the lung-draining mediastinal lymph nodes (medLNs) of virus-infected mice. In contrast, conventional CD4(+) T cells with identical TCR specificity underwent little or no conversion to become "adaptive" Tregs. The virus-reactive Tregs in the medLNs and the lungs of infected mice upregulated a variety of molecules associated with Treg activation, as well as acquired expression of molecules (T-bet, Blimp-1, and IL-10) that confer functional specialization to Tregs. Notably, however, the phenotypes of the T-bet(+) Tregs obtained from these sites were distinct, because Tregs isolated from the lungs expressed significantly higher levels of T-bet, Blimp-1, and IL-10 than did Tregs from the medLNs. Adoptive transfer of Ag-reactive Tregs led to decreased proliferation of antiviral CD4(+) and CD8(+) effector T cells in the lungs of infected hosts, whereas depletion of Tregs had a reciprocal effect. These studies demonstrate that thymically generated Tregs can become activated by a pathogen-derived peptide and acquire discrete T-bet(+) Treg phenotypes while participating in and modulating an antiviral immune response.
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http://dx.doi.org/10.4049/jimmunol.1203302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703618PMC
June 2013

Autoreactive Th1 cells activate monocytes to support regional Th17 responses in inflammatory arthritis.

J Immunol 2013 Apr 18;190(7):3134-41. Epub 2013 Feb 18.

The Wistar Institute, Philadelphia, PA 19104, USA.

We have examined mechanisms underlying the formation of pathologic Th17 cells using a transgenic mouse model in which autoreactive CD4(+) T cells recognize influenza virus hemagglutinin (HA) as a ubiquitously expressed self-Ag and induce inflammatory arthritis. The lymph nodes of arthritic mice contain elevated numbers of inflammatory monocytes (iMO) with an enhanced capacity to promote CD4(+) Th17 cell differentiation, and a regional inflammatory response develops in the paw-draining lymph nodes by an IL-17-dependent mechanism. The activation of these Th17-trophic iMO precedes arthritis development and occurs in the context of an autoreactive CD4(+) Th1 cell response. Adoptive transfer of HA-specific CD4(+) T cells into nonarthritic mice expressing HA as a self-Ag similarly led to the formation of Th1 cells and of iMO that could support Th17 cell formation, and, notably, the accumulation of these iMO in the lymph nodes was blocked by IFN-γ neutralization. These studies show that autoreactive CD4(+) Th1 cells directed to a systemically distributed self-Ag can promote the development of a regional Th17 cell inflammatory response by driving the recruitment of Th17-trophic iMO to the lymph nodes.
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http://dx.doi.org/10.4049/jimmunol.1203212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608750PMC
April 2013

[Olfactory reference syndrome: a systematic review].

Rev Neurol 2013 Jan;56(2):65-71

Hospital Clínico Universitario.

Introduction: The olfactory reference syndrome (ORS) is a condition characterized by the false belief that one emits a foul or offensive body odor. There is no consensus on the validity of this syndrome as an independent clinical entity.

Patients And Methods: A systematic review of the literature is done (1966-2011) searching for articles about the ORS that included a case report using PsycINFO, PubMed, Medline and ISI Web of Knowledge. Data obtained from 55 cases were analyzed to evaluate clinical consistency and heuristic value of this syndrome.

Results: The clinical picture is: social avoidance 60%, depressed mood 42%, 46% anxiety and ideas of reference 44%. In 36% of the 55 cases described an event that is identified as a trigger. The most common treatment is first antidepressants, second antipsychotics and thirdly psychotherapy, with an overall efficiency of 39%.

Conclusions: The ORS is a clinically well defined syndrome, which would support the idea of being included in the appendix of DSM-5, as an independent entity. The avoidance behaviour and the traumatic event are the more consistent data. An integrative model is propose. It also presents the clinical description and results of functional magnetic resonance imaging of a clinical case.
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January 2013

Requirement for diverse TCR specificities determines regulatory T cell activity in a mouse model of autoimmune arthritis.

J Immunol 2012 May 26;188(9):4171-80. Epub 2012 Mar 26.

The Wistar Institute, Philadelphia, PA 19104, USA.

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are required to restrain the immune system from mounting an autoaggressive systemic inflammatory response, but why their activity can prevent (or allow) organ-specific autoimmunity remains poorly understood. We have examined how TCR specificity contributes to Treg activity using a mouse model of spontaneous autoimmune arthritis, in which CD4(+) T cells expressing a clonotypic TCR induce disease by an IL-17-dependent mechanism. Administration of polyclonal Tregs suppressed Th17 cell formation and prevented arthritis development; notably, Tregs expressing the clonotypic TCR did not. These clonotypic Tregs exerted Ag-specific suppression of effector CD4(+) T cells using the clonotypic TCR in vivo, but failed to mediate bystander suppression and did not prevent Th17 cells using nonclonotypic TCRs from accumulating in joint-draining lymph nodes of arthritic mice. These studies indicate that the availability of Tregs with diverse TCR specificities can be crucial to their activity in autoimmune arthritis.
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http://dx.doi.org/10.4049/jimmunol.1103598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331886PMC
May 2012

Acute cholecystitis and bacteraemia due to Streptococcus bovis biotype II.

Enferm Infecc Microbiol Clin 2011 Jan 31;29(1):70-1. Epub 2010 Dec 31.

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http://dx.doi.org/10.1016/j.eimc.2010.04.017DOI Listing
January 2011

A theoretical study on the mechanism of the base-promoted decomposition of N-chloro,N-methylethanolamine.

Org Biomol Chem 2009 May 2;7(9):1807-14. Epub 2009 Mar 2.

Chemical Reactivity & Photoreactivity Group, Dept. of Physical Chemistry & Chemical Eng. I, University of A Coruña, Alejandro de la Sota 1, E-15008, A Coruña, Spain.

The first step of the base-promoted decomposition of N-chloro,N-methylethanolamine in aqueous solution (CH3N(Cl)CH2CH2OH + HO- --> imine + Cl- + H2O (+ CH2O) --> amine + aldehyde) is investigated at the MP2/6-31++G(d,p) computing level. Solvation is included by using both a microsolvated model, in which two explicit water molecules simulate the specific solvent effects, and a hybrid cluster-continuum model, by applying a polarized continuum on the previous results, to account for the bulk effect of the solvent. Four alternative pathways (bimolecular fragmentation, Hofmann, Zaitsev and intramolecular eliminations) are possible for the rate-limiting step of this base-promoted decomposition. These reactive processes are bimolecular asynchronous concerted reactions. The common feature of the four pathways is the proton transfer to HO- being more advanced than all other molecular events, whereas imine formation is delayed. Non-reactive cyclic arrangements involving one of the explicit water molecules are found at transition structures of Hofmann and Zaitsev eliminations, such water molecule acting both as H+ donor and acceptor. Although MP2 calculations misjudge the absolute activation Gibbs free energy values, this computational level adequately predicts the enhancement in the decomposition rate due to the presence of the -OH group.
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http://dx.doi.org/10.1039/b820006hDOI Listing
May 2009

In vitro susceptibilities of bloodstream isolates of Candida spp.: results from a multicenter active surveillance program in Andalusia.

Enferm Infecc Microbiol Clin 2009 Nov 23;27(9):518-22. Epub 2009 May 23.

Servicio de Microbiología, Hospital de Valme, Seville, Spain.

Objectives: The aim of this study was to determine the antifungal drug susceptibilities of Candida bloodstream isolates in Andalusia, obtained through a multicenter active laboratory-based surveillance between October 2005 and September 2006.

Methods: One hundred and ninety-seven Candida isolates were collected. The MICs of amphotericin B, fluconazole, itraconazole and voriconazole were established using the Sensititre YeastOne panel. The MICs of posaconazole and caspofungin were determined by Etest.

Results: C. albicans was the most frequently isolated species (49.2%), followed by C. parapsilosis (17.3%), C. tropicalis (15.2%), C. glabrata (13.7%) and C. krusei (3.6%). All strains were inhibited at MICs of or = 64 mg/L) and 7 (3.6%) were considered resistant to itraconazole (MIC > or = 1 mg/L). All the isolates were susceptible to voriconazole and caspofungin.

Conclusion: In our study C. krusei and C. glabrata were identified in over 18% of cases of candidemia. Most clinical isolates of these species are resistant or susceptible-dose-dependent to fluconazole but susceptible to voriconazole and caspofungin. These agents must be used in the empiric treatment of candidemia rather than fluconazole.
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http://dx.doi.org/10.1016/j.eimc.2008.09.013DOI Listing
November 2009

Community-acquired bacteremia and acute cholecystitis due to Enterobacter cloacae: a case report.

J Med Case Rep 2009 Sep 11;3:7417. Epub 2009 Sep 11.

Introduction: Enterobacter cloacae is responsible for 65-75% of all Enterobacter infections, bacteremia being the most common syndrome. The majority of infections are nosocomially acquired and in patients with predisposing factors.

Case Presentation: We present a case of E. cloacae bacteremia secondary to acute cholecystitis in a 60-year-old man with recent diagnosis of cholelithiasis. The diagnosis was established with abdominal echography and positive blood and biliary cultures. The patient was managed successfully with cholecystectomy and antibiotic therapy.

Conclusion: The peculiarity of our case is the development of community-acquired bacteremia due to E. cloacae with a clear infectious focus, as a single agent isolated in several blood cultures, in a patient without severe underlying diseases, prior antimicrobial use or previous hospital admission. Although the majority of Enterobacter spp. infections are nosocomially acquired, primary bacteremia being the most common syndrome, these pathogens may also be responsible for community-acquired cases. Patients without predisposing factors may also be affected.
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http://dx.doi.org/10.4076/1752-1947-3-7417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827163PMC
September 2009

[Nasosinusal endoscopic surgery as major out-patient surgery].

Acta Otorrinolaringol Esp 2008 Feb;59(2):57-61

Servicio de Otorrinolaringología, Hospital de Fuenlabrada, Fuenlabrada, Madrid, España.

Introduction: Functional endoscopic sinus surgery (FESS) is a useful and widespread technique that allows the treatment of a large number of nasal pathologies. Nevertheless, although many ENT operations are carried out on an out-patient basis, FESS procedures commonly require at least 1 day of hospital admission in many centres.

Objectives: To evaluate our experience in FESS as day-case, to study causes of unexpected overnight admission, and to identify any risk factors for failing to comply with early discharge.

Material And Method: We studied 145 patients consecutively subjected to out-patient FESS procedures for chronic rhinosinusitis, antrochoanal polyps, and dacryocystorhinostomy from August 2004 to June 2007. We analyzed sex, age, medical history (arterial hypertension, asthma, Widal syndrome), pathology, associated septoplasty, extent of the surgery, and revision surgery.

Results: The re-admission rate was 13.1% with the following as the most frequent causes: bleeding (31.6%), requiring only observation in over half the cases (ie, without changing the nasal packing), and dizziness/weakness (36.8%). Only revision surgery was associated with an increase in the re-admission rate (odds ratio, 3.5; 95% CI, 1.2-10.1).

Conclusions: Our experience in FESS for out-patient surgery shows a readmission rate of 13.1 %, although most cases were related to minor complications. The revision surgery was the only variable that could be associated with an increase in re-admission rate.
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February 2008

Myeloperoxidase-catalyzed chlorination: the quest for the active species.

J Inorg Biochem 2008 May-Jun;102(5-6):1300-11. Epub 2008 Jan 9.

Chemical Reactivity and Photoreactivity Group, Department of Physical Chemistry and Chemical Engineering I, University of A Coruña, Alejandro de la Sota 1, E-15008 A Coruña, Spain.

Myeloperoxidase (MPO) is a dominating enzyme of circulating polymorphonuclear neutrophils that catalyzes the two-electron oxidation of chloride, thereby producing the strong halogenating agent hypochlorous acid (ClO(-)/HOCl). In absence of MPO the tripeptide Pro-Gly-Gly reacts with HOCl faster than the amino acid taurine (2-aminoethanesulfonic acid, Tau), while the MPO-mediated chlorination shows reverse order. A comparative study of the enzymatic oxidation of both substrates at pH 4.0-6.0, varying H2O2 concentration is presented. Initial and equilibrium rates studies have been carried on, reaction rates in the latter being slower due to the chemical equilibrium between MPO-I and MPO-II-HO2. A maximum of chlorination rate is observed for Pro-Gly-Gly and Tau when [H2O2] approximately 0.3-0.7 mM and pH approximately 4.5-5.0. Several mechanistic possibilities are considered, the proposed one implies that chlorination takes place via two pathways. One, for bulkier substrates, involves chlorination by free HOCl outside the heme cavity; ClO(-) is released from the active center, diffuses away the heme cavity, and undergoes protonation to HOCl. The other implies the existence of compound I-Cl(-) complex (MPO-I-Cl), capable of chlorinating smaller substrates in the heme pocket. Electronic structure calculations show the size of Pro-Gly-Gly comparable to the available gap in the substrate channel, this tripeptide being unable to reach the active site, and its chlorination is only possible by free HOCl outside the enzyme.
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http://dx.doi.org/10.1016/j.jinorgbio.2008.01.003DOI Listing
July 2008

Nucleotide polymorphism and phenotypic associations within and around the phytochrome B2 Locus in European aspen (Populus tremula, Salicaceae).

Genetics 2008 Apr 3;178(4):2217-26. Epub 2008 Feb 3.

Department of Ecology and Environmental Science, Umeå Plant Science Centre, Umeå University, SE-901 87 Umeå, Sweden.

We investigated the utility of association mapping to dissect the genetic basis of naturally occurring variation in bud phenology in European aspen (Populus tremula). With this aim, we surveyed nucleotide polymorphism in 13 fragments spanning an 80-kb region surrounding the phytochrome B2 (phyB2) locus. Although polymorphism varies substantially across the phyB2 region, we detected no signs for deviations from neutral expectations. We also identified a total of 41 single nucleotide polymorphisms (SNPs) that were subsequently scored in a mapping population consisting of 120 trees. We identified two nonsynonymous SNPs in the phytochrome B2 gene that were independently associated with variation in the timing of bud set and that explained between 1.5 and 5% of the observed phenotypic variation in bud set. Earlier studies have shown that the frequencies of both these SNPs vary clinally with latitude. Linkage disequilibrium across the region was low, suggesting that the SNPs we identified are strong candidates for being causally linked to variation in bud set in our mapping populations. One of the SNPs (T608N) is located in the "hinge region," close to the chromophore binding site of the phyB2 protein. The other SNP (L1078P) is located in a region supposed to mediate downstream signaling from the phyB2 locus. The lack of population structure, combined with low levels of linkage disequilibrium, suggests that association mapping is a fruitful method for dissecting naturally occurring variation in Populus tremula.
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http://dx.doi.org/10.1534/genetics.107.082354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323810PMC
April 2008

Adaptive population differentiation in phenology across a latitudinal gradient in European aspen (Populus tremula, L.): a comparison of neutral markers, candidate genes and phenotypic traits.

Evolution 2007 Dec 1;61(12):2849-60. Epub 2007 Oct 1.

Department of Ecology and Environmental Science, Umeå Plant Science Centre, Umeå University, SE-901 87 Umeå, Sweden.

A correct timing of growth cessation and dormancy induction represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees (Rehfeldt et al. 1999; Horvath et al. 2003; Howe et al. 2003). We have studied the deciduous tree European Aspen (Populus tremula) across a latitudinal gradient and compared genetic differentiation in phenology traits with molecular markers. Trees from 12 different areas covering 10 latitudinal degrees were cloned and planted in two common gardens. Several phenology traits showed strong genetic differentiation and clinal variation across the latitudinal gradient, with Q(ST) values generally exceeding 0.5. This is in stark contrast to genetic differentiation at several classes of genetic markers (18 neutral SSRs, 7 SSRs located close to phenology candidate genes and 50 SNPs from five phenology candidate genes) that all showed F(ST) values around 0.015. We thus find strong evidence for adaptive divergence in phenology traits across the latitudinal gradient. However, the strong population structure seen at the quantitative traits is not reflected in underlying candidate genes. This result fit theoretical expectations that suggest that genetic differentiation at candidate loci is better described by F(ST) at neutral loci rather than by Q(ST) at the quantitative traits themselves.
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http://dx.doi.org/10.1111/j.1558-5646.2007.00230.xDOI Listing
December 2007

Myeloperoxidase-catalyzed taurine chlorination: initial versus equilibrium rate.

Arch Biochem Biophys 2007 Oct 17;466(2):221-33. Epub 2007 Aug 17.

Chemical Reactivity & Photoreactivity Group, Department of Physical Chemistry & Chemical Engineering I, University of A Coruña, Alejandro de la Sota 1, E-15008 A Coruña, Spain.

Myeloperoxidase (MPO) catalyzes the two-electron oxidation of chloride, thereby producing hypochlorous acid (HOCl). Taurine (2-aminoethane-sulfonic acid, Tau) is thought to act as a trap of HOCl forming the long-lived oxidant monochlorotaurine [(N-Cl)-Tau], which participates in pathogen defense. Here, we amend and extend previous studies by following initial and equilibrium rate of formation of (N-Cl)-Tau mediated by MPO at pH 4.0-7.0, varying H(2)O(2) concentration. Initial rate studies show no saturation of the active site under assay conditions (i.e. [H(2)O(2)] > or = 2000 [MPO]). Deceleration of Tau chlorination under equilibrium is quantitatively described by the redox equilibrium established by H(2)O(2)-mediated reduction of compound I to compound II. At equilibrium regime the maximum chlorination rate is obtained at [H(2)O(2)] and pH values around 0.4mM and pH 5. The proposed mechanism includes known acid-base and binding equilibria taking place at the working conditions. Kinetic data ruled out the currently accepted mechanism in which a proton participates in the molecular step (MPO-I+Cl(-)) leading to the formation of the chlorinating agent. Results support the formation of a chlorinating compound I-Cl(-) complex (MPO-I-Cl) and/or of ClO(-), through the former or even independently of it. ClO(-) diffuses away and rapidly protonates to HOCl outside the heme pocket. Smaller substrates will be chlorinated inside the enzyme by MPO-I-Cl and outside by HOCl, whereas bulkier ones can only react with the latter.
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http://dx.doi.org/10.1016/j.abb.2007.07.024DOI Listing
October 2007

Clinal variation in phyB2, a candidate gene for day-length-induced growth cessation and bud set, across a latitudinal gradient in European aspen (Populus tremula).

Genetics 2006 Mar 15;172(3):1845-53. Epub 2005 Dec 15.

Department of Ecology and Environmental Science, Umeå Plant Science Centre, University of Umeå, SE-891 87 Umeå, Sweden.

The initiation of growth cessation and dormancy represents a critical ecological and evolutionary trade-off between survival and growth in most forest trees. The most important environmental cue regulating the initiation of dormancy is a shortening of the photoperiod and phytochrome genes have been implicated in short-day-induced bud set and growth cessation in Populus. We characterized patterns of DNA sequence variation at the putative candidate gene phyB2 in 4 populations of European aspen (Populus tremula) and scored single-nucleotide polymorphisms in an additional 12 populations collected along a latitudinal gradient in Sweden. We also measured bud set from a subset of these trees in a growth chamber experiment. Buds set showed significant clinal variation with latitude, explaining approximately 90% of the population variation in bud set. A sliding-window scan of phyB2 identified six putative regions with enhanced population differentiation and four SNPs showed significant clinal variation. The clinal variation at individual SNPs is suggestive of an adaptive response in phyB2 to local photoperiodic conditions. Three of four SNPs showing clinal variation were located in regions with excessive genetic differentiation, demonstrating that searching for regions of high genetic differentiation can be useful for identifying sites putatively involved in local adaptation.
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http://dx.doi.org/10.1534/genetics.105.047522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456270PMC
March 2006
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