Review: The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to examine neural responses with and without the use of a functional task. Indeed, fMRI has been used in clinical trials and pharmacological research studies. In mental health, it has been used to identify brain areas linked to specific symptoms but also has the potential to help identify possible treatment targets. Despite fMRI's many advantages, such findings are rarely the primary outcome measure in clinical trials or research studies. This article reviews fMRI studies in depression that sought to assess the efficacy and mechanism of action of compounds with antidepressant effects. Our search results focused on selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed treatments for depression and ketamine, a fast-acting antidepressant treatment. Normalization of amygdala hyperactivity in response to negative emotional stimuli was found to underlie successful treatment response to SSRIs as well as ketamine, indicating a potential common pathway for both conventional and fast-acting antidepressants. Ketamine's rapid antidepressant effects make it a particularly useful compound for studying depression with fMRI; its effects on brain activity and connectivity trended toward normalizing the increases and decreases in brain activity and connectivity associated with depression. These findings highlight the considerable promise of fMRI as a tool for identifying treatment targets in depression. However, additional studies with improved methodology and study design are needed before fMRI findings can be translated into meaningful clinical trial outcomes

Implementation Science to Accelerate Clean Cooking for Public Health

Clean cooking has emerged as a major concern for global health and development because of the enormous burden of disease caused by traditional cookstoves and fires. The World Health Organization has developed new indoor air quality guidelines that few homes will be able to achieve without replacing traditional methods with modern clean cooking technologies, including fuels and stoves. However, decades of experience with improved stove programs indicate that the challenge of modernizing cooking in impoverished communities includes a complex, multi-sectoral set of problems that require implementation research. The National Institutes of Health, in partnership with several government agencies and the Global Alliance for Clean Cookstoves, has launched the Clean Cooking Implementation Science Network that aims to address this issue. In this article, our focus is on building a knowledge base to accelerate scale-up and sustained use of the cleanest technologies in low- and middle-income countries. Implementation science provides a variety of analytical and planning tools to enhance effectiveness of clinical and public health interventions. These tools are being integrated with a growing body of knowledge and new research projects to yield new methods, consensus tools, and an evidence base to accelerate improvements in health promised by the renewed agenda of clean cooking.Fil: Rosenthal, Joshua. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Balakrishnan, Kalpana. Sri Ramachandra University; IndiaFil: Bruce, Nigel. University of Liverpool; Reino UnidoFil: Chambers, David. National Institutes of Health. National Cancer Institute; Estados UnidosFil: Graham, Jay. The George Washington University; Estados UnidosFil: Jack, Darby. Columbia University; Estados UnidosFil: Kline, Lydia. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Masera, Omar Raul. Universidad Nacional Autónoma de México; MéxicoFil: Mehta, Sumi. Global Alliance for Clean Cookstoves; Estados UnidosFil: Mercado, Ilse Ruiz. Universidad Nacional Autónoma de México; MéxicoFil: Neta, Gila. National Institutes of Health. National Cancer Institute; Estados UnidosFil: Pattanayak, Subhrendu. University of Duke; Estados UnidosFil: Puzzolo, Elisa. Global LPG Partnership; Estados UnidosFil: Petach, Helen. U.S. Agency for International Development; Estados UnidosFil: Punturieri, Antonello. National Heart, Lung, and Blood Institute; Estados UnidosFil: Rubinstein, Adolfo Luis. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sage, Michael. Centers for Disease Control and Prevention; Estados UnidosFil: Sturke, Rachel. National Institutes Of Health. Fogarty International Center; Estados UnidosFil: Shankar, Anita. University Johns Hopkins; Estados UnidosFil: Sherr, Kenny. University of Washington; Estados UnidosFil: Smith, Kirk. University of California at Berkeley; Estados UnidosFil: Yadama, Gautam. Washington University in St. Louis; Estados Unido

Importance of lysosomal cysteine proteases in lung disease

The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal location and the belief that their function was limited to the terminal degradation of proteins. In the past 10 years, this view has changed as these proteases have been found to have specific functions within cells. This review highlights some of these functions, specifically their roles in matrix remodeling and in regulating the immune response, and their relationship to lung diseases

American thoracic society/national heart, lung, and blood institute asthma-chronic obstructive pulmonary disease overlap workshop report

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma andCOPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions

Country activities of Global Alliance against Chronic Respiratory Diseases (GARD): focus presentations at the 11th GARD General Meeting, Brussels

© Journal of Thoracic Disease. All rights reserved.The Global Alliance against Chronic Respiratory Diseases (GARD) is a voluntary network of national and international organizations, institutions and agencies led by the World Health Organization (WHO), working towards the vision of a world where all people breathe freely (1). GARD is supporting WHO in successfully implementing the WHO’s Global Action Plan for the Prevention and Control of Noncommunicable Diseases (NCDs) 2013–2020. The GARD report on GARD activities is published on a regular basis. Collaboration among GARD countries is critical for sharing experiences and providing technical assistance to developing countries based on each country’s needs (2). The annual GARD meeting is a unique opportunity for assembling all of the GARD participants from developed and developing countries: European countries, North and South American Countries, China, Vietnam as well as Eastern Mediterranean, and African countries. Coordinator for Management of NCDs in the WHO Department for Management of Noncommunicable Diseases, Disability, Violence and Injury Prevention (Cherian Varghese) is present at this meeting. The annual meeting of GARD is a forum for exchanging opinions in order to improve care for chronic respiratory diseases (CRDs) and to achieve the GARD goal—a world where all people breathe freely. Experts—in collaboration with WHO—are helping developing countries to achieve their projects regarding teaching, research and programming for CRD. Each year, there is a poster presentation session on country activities. Each participant is able to present his/her country activities that have been achieved since the last meeting. This is followed by discussion. In this paper, we summarize the posters presented during the 11th GARD general meeting. We hope that this will give readers of the GARD section an opportunity to learn for their countries. We can find all posters on the link: https://gard-breathefreely.org/resources-poster/.info:eu-repo/semantics/publishedVersio

Lipid Motif of a Bacterial Antigen Mediates Immune Responses via TLR2 Signaling

The cross-talk between the innate and the adaptive immune system is facilitated by the initial interaction of antigen with dendritic cells. As DCs express a large array of TLRs, evidence has accumulated that engagement of these molecules contributes to the activation of adaptive immunity. We have evaluated the immunostimulatory role of the highly-conserved outer membrane lipoprotein P6 from non-typeable Haemophilus influenzae (NTHI) to determine whether the presence of the lipid motif plays a critical role on its immunogenicity. We undertook a systematic analysis of the role that the lipid motif plays in the activation of DCs and the subsequent stimulation of antigen-specific T and B cells. To facilitate our studies, recombinant P6 protein that lacked the lipid motif was generated. Mice immunized with non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of the lipid motif on P6 was also required for proliferation and cytokine secretion by antigen-specific T cells. Upregulation of T cell costimulatory molecules was abrogated in DCs exposed to non-lipidated rP6 and in TLR2−/− DCs exposed to native P6, thereby resulting in diminished adaptive immune responses. Absence of either the lipid motif on the antigen or TLR2 expression resulted in diminished cytokine production from stimulated DCs. Collectively; our data suggest that the lipid motif of the lipoprotein antigen is essential for triggering TLR2 signaling and effective stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid motif on activating both innate and adaptive immune responses to an otherwise poorly immunogenic protein antigen

“In vitro” evaluation of bone marrow angiogenesis in myelodysplastic syndromes: a functional and immunophenotypical approach.

“In vitro” evaluation of bone marrow angiogenesis in myelodysplastic syndromes: a functional and immunophenotypical approach