Publications by authors named "Jorge Sánchez"

432 Publications

The wisdom of mistrust: qualitative insights from transgender women who participated in PrEP research in Lima, Peru.

J Int AIDS Soc 2021 Sep;24(9):e25769

Department of Medicine, Division of Infectious Diseases, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA.

Introduction: Although pre-exposure prophylaxis (PrEP) is a remarkable biomedical advance to prevent HIV, ongoing research on PrEP contributes to and interacts with a legacy of HIV experimentation on marginalized communities in resource-limited settings. This paper explores the complexity of PrEP research mistrust among Peruvian transgender (trans) women who completed a PrEP adherence intervention and those who refused participation (i.e. declined to enrol, voluntarily withdrew, and/or were lost to follow-up).

Methods: Data were derived from 86 trans women (mean age 29 years) participants in the formative (four focus groups (n = 32), 20 interviews) and the evaluation stages (34 interviews) of a social network-based PrEP intervention for trans women in Lima, Peru. The formative stage took place from May to July 2015, while the evaluative stage took place from April to May 2018. Audio files were transcribed verbatim and analysed via an immersion crystallization approach using Dedoose (v.6.1.18).

Results: Three paradoxes of trans women's participation in PrEP science as a "key" population emerged as amplifying mistrust: (1) increases in PrEP research targeting trans women but limited perceived improvements in HIV outcomes; (2) routine dismissal by research physicians and staff of PrEP-related side effects and the social realities of taking PrEP, resulting in questions about who PrEP research is really for and (3) persistent limitations on PrEP access for trans women despite increasing involvement in clinical trials, fostering feelings of being a "guinea pig" to advance PrEP science.

Conclusions: Findings highlight the wisdom inherent in PrEP mistrust as a reflection of trans women's experiences that underscore the broken bonds of trust between communities, researchers and the research enterprise. PrEP mistrust is amplified through perceived paradoxes that suggest to trans women that they are key experimental participants but not target PrEP users outside of research settings. Findings highlight the urgent need to reframe mistrust not as a characteristic of trans women to be addressed through education and outreach, but as a systemic institutional- and industry-level problem replicated, manifested and ultimately to be corrected, through global HIV science.
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http://dx.doi.org/10.1002/jia2.25769DOI Listing
September 2021

Mouse Models for Human Skin Transplantation: A Systematic Review.

Cells Tissues Organs 2021 14;210(4):250-259. Epub 2021 Sep 14.

Department of Plastic Surgery and Burn Unit, University Hospital of Getafe, Madrid, Spain.

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation.
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http://dx.doi.org/10.1159/000516154DOI Listing
September 2021

Empathy Levels Among Veterinary Medicine Students in Colombia (South America).

J Vet Med Educ 2021 Sep 9:e20210048. Epub 2021 Sep 9.

Empathy plays an important role in veterinarians' relationships with their patients, clients, and colleagues. Because it relates to greater clinical competence and facilitates the acquisition of information for diagnosing, prescribing therapies, and identifying and treating animal pain, empathy is an essential competence to be strengthened during professional training. The objective of this study was to evaluate the empathy levels of veterinary medicine students toward people and animals and to identify associated factors. The animal empathy scale and the Davis interpersonal reactivity index were applied through an electronic survey to first-, third-, and fifth-year students ( = 559) in three veterinarian medical schools in Colombia. A principal components analysis was performed to identify composite scores of human and animal empathy levels. The empathy toward humans total score ranged from 0 to 112, and the empathy toward animals total score was between 22 and 198. The average empathy scores for students were 89.67 ± 9.02 (mean ± SD; range: 60-115) and 115.01 ± 13.41 (mean ± SD; range: 67-165), respectively. The results suggest that empathy scores toward people are acceptable. Gender, university, program type, age, year of study, and diet were significantly associated with empathy levels toward animals. It is proposed that levels of empathy toward animals be strengthened by fostering a positive learning environment, developing ethical and animal welfare competencies, and increasing empathetic contact and hands-on experience with animals during the curriculum.
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http://dx.doi.org/10.3138/jvme-2021-0048DOI Listing
September 2021

Presence of IgE Autoantibodies Against Eosinophil Peroxidase and Eosinophil Cationic Protein in Severe Chronic Spontaneous Urticaria and Atopic Dermatitis.

Allergy Asthma Immunol Res 2021 Sep;13(5):746-761

Group of Clinical and Experimental Allergy, IPS Universitaria Clinic, University of Antioquia, Medellín, Colombia.

Purpose: Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD.

Methods: We recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using tools.

Results: The frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels ( = 0.542, < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. analysis showed a possible shared epitope in the peroxidase protein family.

Conclusions: IgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.
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http://dx.doi.org/10.4168/aair.2021.13.5.746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419645PMC
September 2021

The Unmet Needs in Atopic Dermatitis Control in Latin America: A Multidisciplinary Expert Perspective.

Dermatol Ther (Heidelb) 2021 Oct 27;11(5):1521-1540. Epub 2021 Aug 27.

Attending Dermatology Department, Hospital Nacional de Niños Costa Rica, Universidad de Costa Rica y Universidad Latina de Costa Rica, San José, Costa Rica.

Introduction: Adoption of control tools for atopic dermatitis (AD) in Latin America (LA) is currently very limited. Clinical assessment tools represent a practical method to measure the impact of treatment on disease activity and on the quality of life of patients. However, the use of these tools in the LA clinical practice setting is limited.

Methods: A selected panel of Latin American experts in fields related to atopic dermatitis were provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion, until a consensus was achieved.

Results: The panel proposes specific and realistic recommendations for implementing control tools for AD care in LA. In creating these recommendations, the authors strove to address all barriers to the widespread use of these tools.

Conclusion: This article includes a narrative analysis of barriers to AD control in LA and provides necessary recommendations to integrate and increase the use of validated AD control assessment tools throughout the region.
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http://dx.doi.org/10.1007/s13555-021-00595-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395384PMC
October 2021

Using Machine Learning to Characterize Atrial Fibrotic Substrate From Intracardiac Signals With a Hybrid and Dataset.

Front Physiol 2021 5;12:699291. Epub 2021 Jul 5.

Institute of Biomedical Engineering, Karlsruhe Institute for Technology, Karlsruhe, Germany.

In patients with atrial fibrillation, intracardiac electrogram signal amplitude is known to decrease with increased structural tissue remodeling, referred to as fibrosis. In addition to the isolation of the pulmonary veins, fibrotic sites are considered a suitable target for catheter ablation. However, it remains an open challenge to find fibrotic areas and to differentiate their density and transmurality. This study aims to identify the volume fraction and transmurality of fibrosis in the atrial substrate. Simulated cardiac electrograms, combined with a generalized model of clinical noise, reproduce clinically measured signals. Our hybrid dataset approach combines and clinical electrograms to train a decision tree classifier to characterize the fibrotic atrial substrate. This approach captures different dynamics of the electrical propagation reflected on healthy electrogram morphology and synergistically combines it with synthetic fibrotic electrograms from experiments. The machine learning algorithm was tested on five patients and compared against clinical voltage maps as a proof of concept, distinguishing non-fibrotic from fibrotic tissue and characterizing the patient's fibrotic tissue in terms of density and transmurality. The proposed approach can be used to overcome a single voltage cut-off value to identify fibrotic tissue and guide ablation targeting fibrotic areas.
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http://dx.doi.org/10.3389/fphys.2021.699291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287829PMC
July 2021

The openCARP simulation environment for cardiac electrophysiology.

Comput Methods Programs Biomed 2021 Sep 8;208:106223. Epub 2021 Jun 8.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, F-33600 Pessac-Bordeaux, France; Université Bordeaux, IMB, UMR 5251, F-33400 Talence, France.

Background And Objective: Cardiac electrophysiology is a medical specialty with a long and rich tradition of computational modeling. Nevertheless, no community standard for cardiac electrophysiology simulation software has evolved yet. Here, we present the openCARP simulation environment as one solution that could foster the needs of large parts of this community.

Methods And Results: openCARP and the Python-based carputils framework allow developing and sharing simulation pipelines which automate in silico experiments including all modeling and simulation steps to increase reproducibility and productivity. The continuously expanding openCARP user community is supported by tailored infrastructure. Documentation and training material facilitate access to this complementary research tool for new users. After a brief historic review, this paper summarizes requirements for a high-usability electrophysiology simulator and describes how openCARP fulfills them. We introduce the openCARP modeling workflow in a multi-scale example of atrial fibrillation simulations on single cell, tissue, organ and body level and finally outline future development potential.

Conclusion: As an open simulator, openCARP can advance the computational cardiac electrophysiology field by making state-of-the-art simulations accessible. In combination with the carputils framework, it offers a tailored software solution for the scientific community and contributes towards increasing use, transparency, standardization and reproducibility of in silico experiments.
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http://dx.doi.org/10.1016/j.cmpb.2021.106223DOI Listing
September 2021

CVAR-Seg: An Automated Signal Segmentation Pipeline for Conduction Velocity and Amplitude Restitution.

Front Physiol 2021 24;12:673047. Epub 2021 May 24.

Institute of Biomedical Engineering (IBT), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.

Background: Rate-varying S1S2 stimulation protocols can be used for restitution studies to characterize atrial substrate, ionic remodeling, and atrial fibrillation risk. Clinical restitution studies with numerous patients create large amounts of these data. Thus, an automated pipeline to evaluate clinically acquired S1S2 stimulation protocol data necessitates consistent, robust, reproducible, and precise evaluation of local activation times, electrogram amplitude, and conduction velocity. Here, we present the CVAR-Seg pipeline, developed focusing on three challenges: (i) No previous knowledge of the stimulation parameters is available, thus, arbitrary protocols are supported. (ii) The pipeline remains robust under different noise conditions. (iii) The pipeline supports segmentation of atrial activities in close temporal proximity to the stimulation artifact, which is challenging due to larger amplitude and slope of the stimulus compared to the atrial activity.

Methods And Results: The S1 basic cycle length was estimated by time interval detection. Stimulation time windows were segmented by detecting synchronous peaks in different channels surpassing an amplitude threshold and identifying time intervals between detected stimuli. Elimination of the stimulation artifact by a matched filter allowed detection of local activation times in temporal proximity. A non-linear signal energy operator was used to segment periods of atrial activity. Geodesic and Euclidean inter electrode distances allowed approximation of conduction velocity. The automatic segmentation performance of the CVAR-Seg pipeline was evaluated on 37 synthetic datasets with decreasing signal-to-noise ratios. Noise was modeled by reconstructing the frequency spectrum of clinical noise. The pipeline retained a median local activation time error below a single sample (1 ms) for signal-to-noise ratios as low as 0 dB representing a high clinical noise level. As a proof of concept, the pipeline was tested on a CARTO case of a paroxysmal atrial fibrillation patient and yielded plausible restitution curves for conduction speed and amplitude.

Conclusion: The proposed openly available CVAR-Seg pipeline promises fast, fully automated, robust, and accurate evaluations of atrial signals even with low signal-to-noise ratios. This is achieved by solving the proximity problem of stimulation and atrial activity to enable standardized evaluation without introducing human bias for large data sets.
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http://dx.doi.org/10.3389/fphys.2021.673047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181407PMC
May 2021

Clinical Relevance of Shrimp Sensitization in Patients with Allergic Rhinitis: Anti-Der p 10 IgE as Predictor.

Int Arch Allergy Immunol 2021 4;182(10):971-979. Epub 2021 Jun 4.

Group of Clinical and Experimental Allergy (GACE), "IPS Universitaria" Clinic, University of Antioquia, Medellín, Colombia.

Introduction: Cross-reactivity between shrimp and house dust mite (HDM) proteins has been widely documented. In tropical region, shrimp (5-15%) and mite sensitization (80-95%) is prevalent in allergic patients. However, the clinical relevance of shrimp sensitization in patients with allergic rhinitis (AR) has been poorly studied. The aim of this study was to determine the prevalence and the clinical relevance shrimp IgE sensitization in AR patients sensitized to Dermatophagoides pteronyssinus.

Methods: The study was conducted in Medellin (Colombia). A cross-sectional study in patients with AR sensitized to HDM was performed in 3 steps: (i) assessment of IgE sensitization frequency to shrimp Penaeus azteca, Litopenaeus vannamei, and tropomyosin homologous allergens rDer p 10, rPen a 1, and rLit v 1, (ii) evaluation of the clinical relevance of shrimp sensitization using oral challenge test (OCT) and (iii) identification of possible risk factors for positive-OCT results. Ethical committee approval was obtained.

Results: From 443 patients with AR, 86 (19.4%) were sensitized to shrimp and 23 of them (26.7%) had shrimp allergy diagnosis. Thirty-six of the patients sensitized to shrimp (41.2%) reported not previously consumed this food and eleven of them had a positive-OCT (30.5%). There was not statistically significant difference in total IgE or sIgE (D. pteronyssinus, P. azteca, L. vannamei, rPen a 1, and rLit v 1) between OCT groups (positive vs. negative results). Anti-Der p 10 IgE was associated with risk for a positive-OCT in different multivariable scenarios.

Discussion/conclusion: Our results suggest that in patients with HDM-associated AR and shrimp IgE sensitization is necessary to evaluate the clinical relevance of shrimp IgE even if the patient has never consumed shrimp because of cross-reactivity. Anti-Der p 10 could be a possible biomarker of clinical relevance to shrimp sensitization and could reduce the need for OCTs.
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http://dx.doi.org/10.1159/000516005DOI Listing
June 2021

analysis of cross reactivity among phospholipases from Hymenoptera species.

F1000Res 2021 5;10. Epub 2021 Jan 5.

Health Faculty - GINUMED, Corporation University Rafael Nuñez, Cartagena, Colombia.

Phospholipases are enzymes with the capacity to hydrolyze membrane lipids and have been characterized in several allergenic sources, such as hymenoptera species. However, cross-reactivity among phospholipases allergens are little understood. The objective of this study was to determine potential antigenic regions involved in cross-reactivity among allergens of phospholipases using an approach. In total, 18 amino acids sequences belonging to phospholipase family derived from species of the order hymenoptera were retrieved from the UniProt database to perform phylogenetic analysis to determine the closest molecular relationship. Multialignment was done to identify conserved regions and matched with antigenic regions predicted by ElliPro server. 3D models were obtained from modeling by homology and were used to locate cross-reactive antigenic regions. Phylogenetic analysis showed that the 18 phospholipases split into four monophyletic clades (named here as A, B, C and D). Phospholipases from A clade shared an amino acid sequences' identity of 79%. Antigenic patches predicted by Ellipro were located in highly conserved regions, suggesting that they could be involved in cross-reactivity in this group (Ves v 1, Ves a 1 and Ves m 1). At this point, we advanced to the characterization of potential antigenic sites involved in cross-reactivity among phospholipases. Inhibition assays are needed to confirm our finding.
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http://dx.doi.org/10.12688/f1000research.27089.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129813PMC
June 2021

A global metagenomic map of urban microbiomes and antimicrobial resistance.

Cell 2021 Jun 26;184(13):3376-3393.e17. Epub 2021 May 26.

Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA.

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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http://dx.doi.org/10.1016/j.cell.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238498PMC
June 2021

Host Transcriptome and Microbiota Signatures Prior to Immunization Profile Vaccine Humoral Responsiveness.

Front Immunol 2021 10;12:657162. Epub 2021 May 10.

Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.

The identification of new biomarkers is essential to predict responsiveness to vaccines. We investigated the whole-blood transcriptome and microbiome prior to immunization, in order to assess their involvement in induction of humoral responses two months later. We based our analyses on stool and skin microbiota, and blood transcriptome prior to immunization, in a randomized clinical study in which participants were vaccinated with the MVA-HIV clade B vaccine (MVA-B). We found that the levels of neutralizing antibody responses were correlated with abundance of in stool and in skin. In addition, genus diversity and bacterial species abundance were also correlated with the expression of genes involved in B cell development prior to immunization and forecast strong responders to MVA-B. To our knowledge, this is the first study integrating host blood gene expression and microbiota that might open an avenue of research in this field and to optimize vaccination strategies and predict responsiveness to vaccines.
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http://dx.doi.org/10.3389/fimmu.2021.657162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141841PMC
September 2021

Linkage to care after HIV diagnosis among men who have sex with men and transgender women in Lima, Peru.

AIDS Care 2021 May 20:1-5. Epub 2021 May 20.

Vaccine and Infectious Disease & Public Health Science Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage within 90 days of HIV diagnosis by matching data from two studies conducted in Lima between 2013 and 2015 to national ART program records. We used generalized linear modeling to assess predictors of timely linkage and late presentation to care. Of 487 newly-diagnosed MSM and TW, only 44% presented for care at an HIV clinic within 90 days. Timely linkage was less common among TW (aPR 0.7, 95% CI 0.5-1.0), those younger than 24 (aPR 0.8, 95% CI 0.6-1.0), and those reporting a history of sex work (aPR 0.7, 95% CI 0.6-0.9). Proximity to an ART program clinic was not associated with linkage; most participants linked to clinics offering "LGBTQ-friendly" care. The pattern of clinics selected by participants suggests the importance of concerns about confidentiality and stigma in decision-making about where to link to care.
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http://dx.doi.org/10.1080/09540121.2021.1929818DOI Listing
May 2021

Direct Visualization of TAVR-Related Coronary Artery Management Techniques in Reanimated Beating Hearts.

JACC Cardiovasc Interv 2021 May;14(9):e87-e91

Visible Heart Laboratories, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

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http://dx.doi.org/10.1016/j.jcin.2021.02.045DOI Listing
May 2021

Cycle length statistics during human atrial fibrillation reveal refractory properties of the underlying substrate: a combined in silico and clinical test of concept study.

Europace 2021 03;23(23 Suppl 1):i133-i142

Department of Electrical Engineering and Information Technology, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Kaiserstr. 12, 76131 Karlsruhe, Germany.

Aims: The treatment of atrial fibrillation beyond pulmonary vein isolation has remained an unsolved challenge. Targeting regions identified by different substrate mapping approaches for ablation resulted in ambiguous outcomes. With the effective refractory period being a fundamental prerequisite for the maintenance of fibrillatory conduction, this study aims at estimating the effective refractory period with clinically available measurements.

Methods And Results: A set of 240 simulations in a spherical model of the left atrium with varying model initialization, combination of cellular refractory properties, and size of a region of lowered effective refractory period was implemented to analyse the capabilities and limitations of cycle length mapping. The minimum observed cycle length and the 25% quantile were compared to the underlying effective refractory period. The density of phase singularities was used as a measure for the complexity of the excitation pattern. Finally, we employed the method in a clinical test of concept including five patients. Areas of lowered effective refractory period could be distinguished from their surroundings in simulated scenarios with successfully induced multi-wavelet re-entry. Larger areas and higher gradients in effective refractory period as well as complex activation patterns favour the method. The 25% quantile of cycle lengths in patients with persistent atrial fibrillation was found to range from 85 to 190 ms.

Conclusion: Cycle length mapping is capable of highlighting regions of pathologic refractory properties. In combination with complementary substrate mapping approaches, the method fosters confidence to enhance the treatment of atrial fibrillation beyond pulmonary vein isolation particularly in patients with complex activation patterns.
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http://dx.doi.org/10.1093/europace/euaa404DOI Listing
March 2021

IgE, blood eosinophils and FeNO are not enough for choosing a monoclonal therapy among the approved options in patients with type 2 severe asthma.

World Allergy Organ J 2021 Mar 5;14(3):100520. Epub 2021 Mar 5.

Clinical and Experimental Allergology Group, Clinic "IPS Universitaria", University of Antioquia, Medellín, Colombia.

Type-2 inflammation is the most frequent endophenotype of asthma. Different biomarkers have been proposed to identify this inflammation because highly effective therapies have improved type-2 severe asthma control. We investigated the frequency of some biomarkers of type-2 inflammation (total IgE, sIgE, blood eosinophil, and FeNO) in the framework of severe asthma and assessed its ability to help us to choose the best biological therapy for each patient. Different scenarios (sensitivity analysis) were evaluated according to the biomarkers proposed for each biological therapy in 72 patients with type-2 severe asthma. Between 54.1% and 68% of patients could receive at least 2 different biological therapies and 34.7%-40.2% could receive any of the 3 types of therapies (anti-IgE, anti-eosinophil, anti-IL4). Biomarkers help to identify type-2 severe asthma but total IgE, sIgE, blood eosinophil, and FeNO are not enough to select 1 specific therapy. With the increasing arrival of new biological therapies, it is necessary to identify new biomarkers that allow us to improve our selection criteria for the best therapy for each patient or to construct a prediction rule.
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http://dx.doi.org/10.1016/j.waojou.2021.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941083PMC
March 2021

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

N Engl J Med 2021 03;384(11):1003-1014

From the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (L.C., P.B.G., M.J., S.T.K., A.C.C., E.R., Y.H., K.E.M., J. Hural, M.J.M.E., C.B., S.T., N.E., A.K.R., N.K., D.J.D., J.G.K., G.G.), and the Departments of Global Health, Microbiology, and Medicine, University of Washington (J.I.M.), Seattle; the Department of Surgery and Duke Human Vaccine Institute, Duke University Medical Center (D.C.M.), and FHI 360 (N.S., P.A.), Durham, and the Institute for Global Health and Infectious Disease, University of North Carolina, Chapel Hill (M.S.C.) - both in North Carolina; the National Institute for Communicable Diseases of the National Health Laboratory Service (L.M.) and the Antibody Immunity Research Unit, Faculty of Health Sciences (L.M.), and the Perinatal HIV Research Unit, Faculty of Health Sciences (F.L., E.M.L., S.T.), University of the Witwatersrand, Johannesburg, the Desmond Tutu HIV Centre, Department of Medicine and Institute of Infectious Disease and Molecular Medicine (C.O.), and the Division of Medical Virology (C.W.), University of Cape Town, Cape Town, the School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria (S.T.), and the South African Medical Research Council, Tygerberg (G.G.) - all in South Africa; the Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta (S.E.); the University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe (N.M.M., P.G.M.); Servicio de Enfermedades Infecciosas y Tropicales, Hospital Nacional Dos de Mayo (P.G.), Asociación Civil Via Libre (R.C.), Asociación Civil Impacta Salud y Educación (J.R.L.), and Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, Universidad Nacional Mayor de San Marcos (J.S.), Lima, and Association Civil Selva Amazónica, Clinical Research Site, Iquitos (J. Hinojosa) - both in Peru; the Infectious Diseases Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (I.F.); the Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York (M.E.S.); Botswana Harvard AIDS Institute, Gaborone, Botswana (J.M.); Brigham and Women's Hospital, Harvard Medical School, Boston (L.R.B.); and the Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Rockville (M.M.G.L.), the Prevention Sciences Program, Division of AIDS (D.N.B.), and the Vaccine Research Center (J.E.L., J.R.M.), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, and Johns Hopkins University School of Medicine, Baltimore (E.P.-M.) - all in Maryland.

Background: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.

Methods: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC) of acquired isolates was measured with the TZM-bl assay.

Results: Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates.

Conclusions: VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).
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http://dx.doi.org/10.1056/NEJMoa2031738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189692PMC
March 2021

Does Antigen Glycosylation Impact the HIV-Specific T Cell Immunity?

Front Immunol 2020 22;11:573928. Epub 2021 Jan 22.

IrsiCaixa-AIDS Research Institute, Badalona, Spain.

It is largely unknown how post-translational protein modifications, including glycosylation, impacts recognition of self and non-self T cell epitopes presented by HLA molecules. Data in the literature indicate that - and -linked glycosylation can survive epitope processing and influence antigen presentation and T cell recognition. In this perspective, we hypothesize that glycosylation of viral proteins and processed epitopes contribute to the T cell response to HIV. Although there is some evidence for T cell responses to glycosylated epitopes (glyco-epitopes) during viral infections in the literature, this aspect has been largely neglected for HIV. To explore the role of glyco-epitope specific T cell responses in HIV infection we conducted and immune studies in individuals with chronic HIV infection. We found that viral protein segments with potentially glycosylable epitopes were less frequently targeted by T cells. synthetically added glycosylation moieties generally masked T cell recognition of HIV derived peptides. Nonetheless, in some cases, addition of simple glycosylation moieties produced neo-epitopes that were recognized by T cells from HIV infected individuals. Herein, we discuss the potential importance of these observations and compare limitations of the employed technology with new methodologies that may have the potential to provide a more accurate assessment of glyco-epitope specific T cell immunity. Overall, this perspective is aimed to support future research on T cells recognizing glycosylated epitopes in order to expand our understanding on how glycosylation of viral proteins could alter host T cell immunity against viral infections.
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http://dx.doi.org/10.3389/fimmu.2020.573928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862545PMC
June 2021

In vivo nanoscale analysis of the dynamic synergistic interaction of Bacillus thuringiensis Cry11Aa and Cyt1Aa toxins in Aedes aegypti.

PLoS Pathog 2021 01 19;17(1):e1009199. Epub 2021 Jan 19.

Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, Mexico.

The insecticidal Cry11Aa and Cyt1Aa proteins are produced by Bacillus thuringiensis as crystal inclusions. They work synergistically inducing high toxicity against mosquito larvae. It was proposed that these crystal inclusions are rapidly solubilized and activated in the gut lumen, followed by pore formation in midgut cells killing the larvae. In addition, Cyt1Aa functions as a Cry11Aa binding receptor, inducing Cry11Aa oligomerization and membrane insertion. Here, we used fluorescent labeled crystals, protoxins or activated toxins for in vivo localization at nano-scale resolution. We show that after larvae were fed solubilized proteins, these proteins were not accumulated inside the gut and larvae were not killed. In contrast, if larvae were fed soluble non-toxic mutant proteins, these proteins were found inside the gut bound to gut-microvilli. Only feeding with crystal inclusions resulted in high larval mortality, suggesting that they have a role for an optimal intoxication process. At the macroscopic level, Cry11Aa completely degraded the gastric caeca structure and, in the presence of Cyt1Aa, this effect was observed at lower toxin-concentrations and at shorter periods. The labeled Cry11Aa crystal protein, after midgut processing, binds to the gastric caeca and posterior midgut regions, and also to anterior and medium regions where it is internalized in ordered "net like" structures, leading finally to cell break down. During synergism both Cry11Aa and Cyt1Aa toxins showed a dynamic layered array at the surface of apical microvilli, where Cry11Aa is localized in the lower layer closer to the cell cytoplasm, and Cyt1Aa is layered over Cry11Aa. This array depends on the pore formation activity of Cry11Aa, since the non-toxic mutant Cry11Aa-E97A, which is unable to oligomerize, inverted this array. Internalization of Cry11Aa was also observed during synergism. These data indicate that the mechanism of action of Cry11Aa is more complex than previously anticipated, and may involve additional steps besides pore-formation activity.
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http://dx.doi.org/10.1371/journal.ppat.1009199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846010PMC
January 2021

TransPrEP: Results from the Pilot Study of a Social Network-Based Intervention to Support PrEP Adherence Among Transgender Women in Lima, Peru.

AIDS Behav 2021 Jun 1;25(6):1873-1883. Epub 2021 Jan 1.

Asociacion Civil Impacta Salud y Educacion, Lima, Peru.

We conducted a pilot randomized controlled trial of a social network-based intervention to promote PrEP adherence among transgender women (TW) in Lima, Peru. We enrolled 89 TW from six social networks and cluster-randomized them 1:1 to standard of care (n = 44) or the TransPrEP intervention (n = 45). Core workshops discussed strategies to support PrEP adherence and defined group adherence objectives. Maintenance workshops discussed participants' experiences taking PrEP and collective adherence goals. At 3-month follow-up, we evaluated 40 participants and obtained 29 hair samples for tenofovir level measurements. Though no significant differences were observed, 36.4% (4/11) of participants of TransPrEP participants and 10.0% (1/10) of control participants had tenofovir levels > 0.023 ng/mg, consistent with ≥ 4 doses per week. 81.8% (9/11) of intervention and 40.0% (4/10) of control participants had any detectable tenofovir in their hair. Pilot assessment of our network-based intervention suggested a trend towards improved PrEP adherence, measured objectively, for TW in Peru.
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http://dx.doi.org/10.1007/s10461-020-03117-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084919PMC
June 2021

Simple Nephrectomy in a Tertiary Care Safety Net Hospital-Patient Characteristics, Causes, Cost, and Renal Function Implications.

Urology 2021 Mar 24;149:98-102. Epub 2020 Dec 24.

Division of Urology, John Peter Smith Hospital, Fort Worth, TX; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:

Objective: To evaluate factors associated with simple nephrectomy at a safety net hospital with a diverse patient population and large catchment area. Simple nephrectomy is an underreported surgery. Performance of simple nephrectomy may represent a failure of management of underlying causes.

Methods: We performed a retrospective review of simple nephrectomies performed at a major urban safety net hospital from 2014 to 2019. Detailed demographic, surgical, and renal functional outcomes were abstracted. We assessed the medical and social factors leading to performance of simple nephrectomy and report contemporaneous perception of preventability of the simple nephrectomy by the surgeon.

Results: Eighty-five patients underwent simple nephrectomy during the study period; 55% were non-white, 77% were women, and the median age at time of surgery was 46 years. The most common medical factors contributing to simple nephrectomy were stone disease in 55.3%, followed by retained ureteral stent (30.6%) and stricture (30.6%). The most common social factors were lack of insurance (58.5%), substance abuse issues (32.3%), mental health issues (24.6%), and immigration status (18.5%). In 38.8% of cases, the provider felt the surgery was preventable if medical factors leading to simple nephrectomy were properly addressed.

Conclusions: Simple nephrectomy is a common surgery in the safety net hospital setting. Both medical and sociologic factors can lead to simple nephrectomy, and awareness of these factors can lead efforts to mitigate them. This review has led to the implementation of strategies to minimize occurrences of retained stents in our patients.
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http://dx.doi.org/10.1016/j.urology.2020.12.013DOI Listing
March 2021

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Iceberg Indicators for Animal Welfare in Rural Sheep Farms Using the Five Domains Model Approach.

Animals (Basel) 2020 Dec 2;10(12). Epub 2020 Dec 2.

Department of Animal Health, Faculty of Agrarian and Animal Sciences, University of Caldas, Manizales 170004, Colombia.

Animal welfare for sheep in extensive rural farms is difficult to quantify among rural farmers due to several factors, including the lack of technology and the low level of interaction they have with the animals. The purpose of this study was to search for animal-based iceberg indicators using the Five Domains Model approach and study the relationship between sheep reactive behavior (flight distance), sheep handling training and farmers job satisfaction. Thirteen extensive commercial dual-purpose sheep farms ( = 520 animals) were evaluated in Marulanda, Caldas (Colombia, South America). On-farm Animal Welfare Indicators (AWIN) were assessed using an adapted version of this protocol. Socio-demographic characteristics, sheep handling training and job satisfaction were evaluated using a structured interview. Blood and stool samples were taken to determine Fecal Egg Count and Packed Cell Volume. Bivariate regression models were used to find animal-based indicators that predicted Nutrition, Ambience, Health and Behavior welfare domains, and a Qualitative Behavior Analysis was used for mind state domain analysis. Body condition score (BCS) ( = 0.001), fleece cleanliness ( = 0.03), FAMACHA© Score ( = 0.05), and flight distance in meters ( = 0.19) were found to be indicators, and were useful for predicting overall welfare assessment (R2 = 0.85) on theses farms. Regarding mind welfare domain, Qualitative Behavioral Assessment found two principal components (PC) that explained 82% and 67% of the variance, and described emotional valence and energy levels of sheep, respectively. Sheep handling training (β = -8.75, = 0.004) and job satisfaction (β = -7.5, = 0.013) had a negative association with the average flock flight distance. Spearman's rank correlations were significant ( < 0.001) between Fecal Egg Count, Packed Cell Volume, FAMACHA© Score (FS), Body Weight (BW) and, BCS. The strongest association was observed between Packed Cell Volume (PCV) and Fecal Egg Count (FEC) ( = -0.43), also FS was correlated with PCV ( = -0.28) and FEC ( = 0.21), and BCS was correlated with weight ( = 0.32). We suggest that these animal-based indicators could be useful as iceberg indicators for extensive sheep production systems and may set the ground for more research in small extensive sheep farms to develop strategies to find welfare problems and solutions.
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http://dx.doi.org/10.3390/ani10122273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760869PMC
December 2020

Dantrolene hinders dengue virus-induced upregulation and translocation of calmodulin to cardiac cell nuclei.

Virology 2021 Jan 21;553:81-93. Epub 2020 Nov 21.

Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico. Electronic address:

Dengue virus (DENV) infection elevates intracellular Ca concentration ([Ca]), but it is unknown whether Ca and calmodulin (CaM) are involved in DENV infection. We conducted immunofluorescence and western blot experiments and measured [Ca] examining the effects of DENV infection and drugs that alter Ca/CaM functions on CaM translocation, DENV2 infection, protein expression, virus-inducible STAT2 protein abundance, and CREB phosphorylation in H9c2 cells. DENV infection increased CaM expression, its nuclear translocation and NS3 and E viral proteins expression and colocalization in a manner that could be blocked by the ryanodine receptor antagonist dantrolene. DENV infection also increased CREB phosphorylation, an effect inhibited by either dantrolene or the CaM inhibitor W7. Dantrolene substantially hindered infection as assessed by focus assays in Vero cells. These results suggest that Ca and CaM play an important role in DENV infection of cardiac cells and that dantrolene may protect against severe DENV cardiac morbidity.
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http://dx.doi.org/10.1016/j.virol.2020.11.005DOI Listing
January 2021

Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study.

Front Immunol 2020 10;11:586124. Epub 2020 Nov 10.

Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMIParis), Paris, France.

Background: Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.

Methods: In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity.

Results: We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response.

Conclusion: Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity.

Clinical Trial Registration: http://ClinicalTrials.gov, identifier PER-073-13.
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http://dx.doi.org/10.3389/fimmu.2020.586124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683801PMC
June 2021

Defining the Histopathological Term Atypical Intraepidermal Melanocytic Proliferation: A Retrospective Cross-Sectional Study.

Am J Dermatopathol 2021 Apr;43(4):252-258

Department of Dermatology, University of Puerto Rico School of Medicine, San Juan, PR.

Background: Atypical intraepidermal melanocytic proliferation (AIMP) is a general term assigned to melanocytic proliferations of uncertain biological potential when a definitive histopathological diagnosis cannot be achieved. There are few data available describing the possibility of malignancy of AIMP, or ways to further define diagnosis.

Objective: To determine the rate of diagnostic change of AIMP to melanoma or melanoma in situ (MIS) after conventional excision. In addition, to determine the role of immunohistochemistry (IHC) in defining AIMP biopsies.

Methods: Retrospective cross-sectional, single-center review of biopsies with a diagnosis of AIMP with a follow-up conventional excision from 2012-2016 was performed. In a separate analysis, a search was performed for AIMP biopsied lesions in which IHC was subsequently performed.

Results: The rate of diagnostic change of AIMP to MIS was 4.8% (8/167) after excision. Punch biopsy was a risk factor for diagnostic change to MIS (odds ratio 12.94, confidence interval 2.56-65.38, P = 0.008). The rate of diagnostic change of AIMP biopsies after examining with IHC was 21.3% (34/160) to MIS and 4.4% (7/160) to melanoma.

Conclusion: The possibility of malignancy of AIMP lesions must be taken into consideration when counseling patients and when planning treatment options. IHC is a useful tool and should be used in the evaluation of AIMP specimens.
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http://dx.doi.org/10.1097/DAD.0000000000001851DOI Listing
April 2021

Sexual Behavior and Sexually Transmitted Infection Outcomes Among Men Who Have Sex With Men and Transgender Women Participating in a Study of the Timing of Antiretroviral Therapy in Lima, Peru.

Sex Transm Dis 2020 12;47(12):825-831

Asociación Civil Impacta Salud y Educación, Lima, Perú.

Background: We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017).

Methods: Sabes participants were tested monthly for HIV to identify acute or early infections, and HIV-positive participants were randomized to receive antiretroviral therapy immediately (immediate arm) or after 24 weeks (deferred arm) during a 48-week follow-up period. Sexual behavior was assessed at randomization (baseline) and every 12 weeks thereafter. Participants were tested for urethral and rectal chlamydia and gonorrhea and for syphilis at baseline, 12, 24, and 48 weeks. We describe patterns of sexual behavior during the 48-week follow-up period and compare sexual behavior and STI incidence between study arms.

Results: After randomization, 207 HIV-positive participants completed questionnaires and STI testing at 2 or more visits. After HIV diagnosis, participants in both arms reported increases in condom use with main and casual partners and decreased drug and alcohol use before or during anal sex. We observed no between-arm differences in sexual behavior. Deferred arm participants had higher incidence of chlamydia (incidence rate ratio, 2.33; 95% confidence interval, 1.14-4.77) but not gonorrhea or syphilis.

Conclusions: Despite reported increases in condom use, the overall high incidence of STIs reflects some ongoing condomless sex among HIV-positive men who have sex with men and transgender women, highlighting the importance of regular STI screening and counseling to support consistent condom use among HIV-positive individuals at risk for STIs.
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http://dx.doi.org/10.1097/OLQ.0000000000001310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672715PMC
December 2020

TL1A-DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1-Specific T Cell Responses.

J Immunol 2020 12 11;205(12):3348-3357. Epub 2020 Nov 11.

Institut de Recerca de la Sida IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, 08916 Barcelona, Spain;

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1-infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cells/mm, = 47) and relatively controlled disease (pVL <10,000 RNA copies/ml; CD4 counts 657 cells/mm, = 49). Our analysis highlighted the TNF molecule's relevance, in particular, TL1A (TNFSF15) and its cognate DR3 (TNFSRF25), both of which increased in the relative virus control phenotype. DR3 levels (in plasma and PBMCs) were validated in unrelated cohorts (including long-term nonprogressors), thus confirming their independence from CD4 counts and pVL. Further analysis in combined antiretroviral treatment (cART)-treated individuals with a wide range of CD4 counts (137-1835 cells/mm) indicated that neither TL1A nor DR3 levels reflected recovery of CD4 counts with cART. Interestingly, in cART-treated individuals, plasma TL1A levels correlated with regulatory T cell frequencies, whereas soluble DR3 was strongly associated with the abundance of effector HLA-DRCD8 T cells. A positive correlation was also observed between plasma DR3 levels and the HIV-1-specific T cell responses. In vitro, costimulation of PBMC with DR3-specific mAb increased the magnitude of HIV-1-specific responses. Finally, in splenocytes of DNA.HTI-vaccinated mice, costimulation of HTI peptides and a DR3 agonist (4C12) intensified the magnitude of T cell responses by 27%. These data describe the role of the TL1A-DR3 axis in the natural control of HIV-1 infection and point to the use of DR3 agonists in HIV-1 vaccine regimens.
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http://dx.doi.org/10.4049/jimmunol.2000933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725879PMC
December 2020

Sexual Behavior Among Men Who Have Sex With Men: The Need for More Targeted Outreach to Men Who Also Have Sex With Cisgender Women.

J Acquir Immune Defic Syndr 2021 03;86(3):265-270

Vaccine and Infectious Disease & Public Health Science Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: In Peru, as in the Americas overall, men who have sex with men (MSM) are disproportionately affected by HIV. Most research focuses on practices between cisgender men, whereas many MSM report male and female partners, cisgender, transgender, or both.

Methods: Data for these analyses were from a treatment-as-prevention study in Lima (the Sabes study). We compared demographics and behaviors of MSM who reported cisgender women partners in the past 3 months (MSMW) and MSM who reported both cisgender and transgender women partners (MSMW-T) to MSM who reported only male partners (MSMO). We calculated HIV incidence in each group during 2-year follow-up.

Results: Compared with MSMO, MSMW and MSMW-T more often self-identify as heterosexual or bisexual and report insertive sex practices. MSMW reported condomless sex with cisgender women: vaginal (72%), anal sex (18%). One-third of MSMW reported condomless receptive anal sex with men in the past 3 months, with 24% of MSMW overall who reported both condomless receptive sex with men and condomless insertive vaginal or anal sex with cisgender women. Of these, 17% were HIV infected. HIV incidence did not differ significantly between groups.

Conclusion: Most MSMW and MSMW-T report bisexual or heterosexual orientation and prefer insertive sex. MSMW and MSMW-T (47% and 29%, respectively) engage in receptive anal intercourse. In both groups, the majority who engaged in condomless receptive sex with men (76% MSMW, 85% MSMW-T) also engaged in condomless vaginal and/or anal sex with women, indicating need for intervention.
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http://dx.doi.org/10.1097/QAI.0000000000002568DOI Listing
March 2021
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