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https://www.readbyqxmd.com/read/28812250/miv-150-and-zinc-acetate-combination-provides-potent-and-broad-activity-against-hiv-1
#1
Olga Mizenina, Mayla Hsu, Ninochka Jean-Pierre, Meropi Aravantinou, Keith Levendosky, Gabriela Paglini, Thomas M Zydowsky, Melissa Robbiani, José A Fernández-Romero
We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs...
August 15, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#2
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28804863/personalised-immunomodulating-treatments-for-graves-disease-fact-or-fiction
#3
Tristan Mirko Struja, Alexander Kutz, Stefan Fischli, Christian Meier, Beat Müller, Philipp Schütz
Although Graves' disease has been recognised for more than 100 years, its physiopathological mechanisms are incompletely understood. Treatment strategies today mainly focus on suppression of thyroid hormone production by use of antithyroid drugs or radio-iodine, but neglect the underlying immunological mechanisms. Although Graves' disease is often seen as a prototype for an autoimmune mechanism, it is more likely to be a heterogeneous syndrome showing characteristics of both autoimmunity and immunodeficiency...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28801449/engraftment-and-in-vivo-proliferation-advantage-of-gene-corrected-mobilized-cd34-cells-from-fanconi-anemia-patients
#4
Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A Casado, Parinda A Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene corrected hematopoietic stem and progenitor cells (HSPC) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34(+) cells from FA-A patients with a therapeutic FANCA-lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells. Transplantation of transduced FA CD34(+) cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid and CD34(+) cells...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28800953/col7a1-editing-via-crispr-cas9-in-recessive-dystrophic-epidermolysis-bullosa
#5
Stefan Hainzl, Patricia Peking, Thomas Kocher, Eva M Murauer, Fernando Larcher, Marcela Del Rio, Blanca Duarte, Markus Steiner, Alfred Klausegger, Johann W Bauer, Julia Reichelt, Ulrich Koller
Designer nucleases allow specific and precise genomic modifications and represent versatile molecular tools for the correction of disease-associated mutations. In this study, we have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach for the correction of a frequent inherited mutation in exon 80 of COL7A1, which impairs type VII collagen expression, causing the severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment of patient-derived keratinocytes, using either the wild-type Cas9 or D10A nickase, corrected single-cell clones expressed and secreted similar levels of type VII collagen as control keratinocytes...
July 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28799824/high-prevalence-of-asymptomatic-sexually-transmitted-infections-among-human-immunodeficiency-virus-infected-pregnant-women-in-a-low-income-south-african-community
#6
Maanda Mudau, Remco P Peters, Lindsey De Vos, Dawie H Olivier, Dvora J Davey, Edwin S Mkwanazi, James A McIntyre, Jeffrey D Klausner, Andrew Medina-Marino
There is a lack of evidence on the burden of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) among HIV-infected pregnant women in South Africa. We conducted a cross-sectional analysis of HIV-infected pregnant women in two healthcare facilities in a South African township to determine the prevalence of CT, NG and TV. HIV-infected pregnant women were recruited during the first antenatal care visit for their current pregnancy and requested to self-collect vulvovaginal swab specimens...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28797489/approach-to-fungal-infections-in-human-immunodeficiency-virus-infected-individuals-pneumocystis-and-beyond
#7
REVIEW
Richard J Wang, Robert F Miller, Laurence Huang
Many fungi cause pulmonary disease in patients with human immunodeficiency virus (HIV) infection. Pathogens include Pneumocystis jirovecii, Cryptococcus neoformans, Aspergillus spp, Histoplasma capsulatum, Coccidioides spp, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Talaromyces marneffei, and Emmonsia spp. Because symptoms are frequently nonspecific, a high index of suspicion for fungal infection is required for diagnosis. Clinical manifestations of fungal infection in HIV-infected patients frequently depend on the degree of immunosuppression and the CD4(+) helper T cell count...
September 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28796758/recommendations-for-hiv-screening-of-gay-bisexual-and-other-men-who-have-sex-with-men-united-states-2017
#8
Elizabeth A DiNenno, Joseph Prejean, Kathleen Irwin, Kevin P Delaney, Kristina Bowles, Tricia Martin, Amrita Tailor, Gema Dumitru, Mary M Mullins, Angela B Hutchinson, Amy Lansky
CDC's 2006 recommendations for human immunodeficiency virus (HIV) testing state that all persons aged 13-64 years should be screened for HIV at least once, and that persons at higher risk for HIV infection, including sexually active gay, bisexual, and other men who have sex with men (MSM), should be rescreened at least annually (1). Authors of reports published since 2006, including CDC (2), suggested that MSM, a group that is at highest risk for HIV infection, might benefit from being screened more frequently than once each year...
August 11, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28791010/uses-of-next-generation-sequencing-technologies-for-the-diagnosis-of-primary-immunodeficiencies
#9
REVIEW
Michael Seleman, Rodrigo Hoyos-Bachiloglu, Raif S Geha, Janet Chou
Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission, and with variable penetrance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28780238/tcr%C3%AE-%C3%AE-and-cd19-cell-depleted-haploidentical-and-mismatched-hematopoietic-stem-cell-transplantation-in-primary-immune-deficiency
#10
Ravi M Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M F Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R Gennery, Paul Veys, Mary Slatter
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved using HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft versus host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD causing TCRαβCD3+ cells from the graft...
August 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28776524/pulmonary-tuberculosis-in-a-pediatric-reference-hospital-in-bogot%C3%A3-colombia
#11
Luisa Fernanda Imbachí Yunda, Eileen Viviana Fonseca Sepúlveda, Kelly Christina Márquez Herrera, Germán Camacho Moreno
BACKGROUND: In Colombia, epidemiological and clinical information related to pediatric tuberculosis (TB) is scarce. Data are needed to define the impact of the disease and to strengthen measures for detection and treatment. It is proposed to analyze the pediatric population diagnosed with pulmonary TB in a national reference institution. METHODS: Retrospective observational study including pediatric patients with pulmonary and miliary TB, and pulmonary and extrapulmonary involvement, treated between January 1, 2008 and December 31, 2016...
July 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28774417/treatment-of-hepatitis-b-virus-with-combination-therapy-now-and-in-the-future
#12
REVIEW
Joel S Emery, Jordan J Feld
Chronic Hepatitis B continues as a significant public health problem despite the availability of safe and effective antivirals and a highly effective protective vaccine. Current therapy, however rarely leads to cure and lifelong therapy is often required, contributing to poor uptake and ongoing morbidity. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
June 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28772262/evolution-and-emergence-of-pathogenic-viruses-past-present-and-future
#13
Mohammad K Parvez, Shama Parveen
Incidences of emerging/re-emerging deadly viral infections have significantly affected human health despite extraordinary progress in the area of biomedical knowledge. The best examples are the recurring outbreaks of dengue and chikungunya fever in tropical and sub-tropical regions, the recent epidemic of Zika in the Americas and the Caribbean, and the SARS, MERS, and influenza A outbreaks across the globe. The established natural reservoirs of human viruses are mainly farm animals, and, to a lesser extent, wild animals and arthropods...
August 4, 2017: Intervirology
https://www.readbyqxmd.com/read/28771777/high-risk-papillomavirus-infection-among-women-living-with-human-immunodeficiency-virus-brazilian-multicentric-study
#14
Angelica E Miranda, Mariangela F Silveira, Ana Gabriela Travassos, Teresinha Tenório, Isabel Cristina Chulvis do Val, Leonor de Lannoy, Hortensio Simões de Mattos Junior, Newton Sergio de Carvalho
BACKGROUND: Cervical cancer is an important health issue in Latin America. Although HPV infections can have spontaneous clearance, persistence of high-risk (HR) HPV is a risk factor for cervical cancer among women and it is even higher in HIV-infected women. OBJECTIVES: to determine the prevalence of HR-HPV and risk factors among HIV-infected women attending reference services for HIV/AIDS in different regions of Brazil. METHODS: Cross-sectional study conducted among HIV-infected women attended at referral care centers for HIV/AIDS in nine states of Brazil...
August 3, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28771456/notes-from-the-field-preliminary-results-after-implementation-of-a-universal-treatment-program-test-and-start-for-persons-living-with-hiv-infection-lesotho-october-2015-february-2017
#15
Amee M Schwitters
Lesotho, a small, mountainous country completely surrounded by the Republic of South Africa, has a population of approximately 2 million persons with an estimated gross national income of $1,280 per capita; 73% of the population resides in rural areas (1). Lesotho has a generalized human immunodeficiency virus (HIV) epidemic (2). In 2014, the prevalence of HIV infection among persons aged 15-49 years was 24.6%, with an incidence of 1.9 new infections per 100 person-years of exposure (3). As the leading cause of premature death, HIV/AIDS (acquired immunodeficiency syndrome) has contributed to Lesotho's reporting the shortest life expectancy at birth among 195 countries and territories (4)...
August 4, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28771116/traditional-health-practitioners-management-of-hiv-aids-in-rural-south-africa-in-the-era-of-widespread-antiretroviral-therapy
#16
Thembelihle Zuma, Daniel Wight, Tamsen Rochat, Mosa Moshabela
BACKGROUND: Traditional health practitioners (THPs) have been identified as a key local resource in the fight against human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) in South Africa. However, their approaches to the treatment of people living with HIV (PLHIV) have been met with scepticism by some biomedical practitioners amid increasing access to antiretroviral therapy (ART). OBJECTIVE: In light of this ambivalence, this study aims to document and identify treatment approaches of THPs to the management of illness among PLHIV in the current era of widespread access to ART...
2017: Global Health Action
https://www.readbyqxmd.com/read/28770278/an-unbiased-in-vivo-functional-genomics-screening-approach-in-mice-identifies-novel-tumor-cell-based-regulators-of-immune-rejection
#17
Casey W Shuptrine, Reham Ajina, Elana J Fertig, Sandra A Jablonski, H Kim Lyerly, Zachary C Hartman, Louis M Weiner
The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. To address this challenge, we developed an unbiased in vivo genome-wide RNAi screening platform that leverages host immune selection in strains of immune-competent and immunodeficient mice to select for tumor cell-based genes that regulate in vivo sensitivity to immune attack...
August 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28770176/inhibition-of-plasmodium-hepatic-infection-by-antiretroviral-compounds
#18
Marta Machado, Margarida Sanches-Vaz, João P Cruz, António M Mendes, Miguel Prudêncio
Recent WHO guidelines on control of human immunodeficiency virus (HIV) call for the widespread use of antiretroviral (AR) therapy (ART) for people living with HIV. Given the considerable overlap between infections by HIV and Plasmodium, the causative agent of malaria, it is important to understand the impact of AR compounds and ART regimens on infections by malaria parasites. We undertook a systematic approach to identify AR drugs and ART drug combinations with inhibitory activity against the obligatory hepatic stage of Plasmodium infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28768877/immunodominance-of-adenovirus-derived-cd8-t-cell-epitopes-interferes-with-the-induction-of-transgene-specific-immunity-in-adenovirus-based-immunization
#19
Dominik Schöne, Camilla Patrizia Hrycak, Sonja Windmann, Dennis Lapuente, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8(+) T cell responses to the encoded transgene. Surprisingly, we found before in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8(+) T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We show now that induction of GagL85-93-specific CD8(+) T cells was highly effective when Leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768817/cxcr4-specific-nanobodies-as-potential-therapeutics-for-whim-syndrome
#20
Raymond H de Wit, Raimond Heukers, Hendrik Brink, Angela Arsova, David Maussang, Pasquale Cutolo, Beatrijs Strubbe, Henry Vischer, Francoise Bachelerie, Martine J Smit
WHIM syndrome is a rare congenital immunodeficiency disease, named after its main clinical manifestations: Warts, Hypogammaglobulinemia, Infections and Myelokathexis. The disease is primarily caused by C-terminal truncation mutations of the chemokine receptor CXCR4. Consequently, these CXCR4-WHIM mutants have a gain of function in response to its ligand CXCL12, which results in abnormal leukocyte migration and thereby immune system dysfunctions. Treatment of WHIM patients currently consists of symptom relief, leading to unsatisfactory clinical responses...
August 2, 2017: Journal of Pharmacology and Experimental Therapeutics
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