No abstract available

Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear.

No abstract available

The National Library of Medicine's (NLM) Division of Specialized Information Services (SIS) Toxicology and Environmental Health Information Program is responsible for the management of the online Hazardous Substances Data Bank (HSDB). HSDB, a part of NLM's Toxicology Data Network (TOXNET(®)), is a file of chemical/substance information with one record for each specific chemical or substance, or for a category of chemicals or substances. Like the rest of TOXNET's databases and other resources, HSDB is available online at no cost to global users. HSDB has approximately 5600 chemicals and substances, with a focus on toxicology information and also on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas of likely interest to HSDB users. All data are from a core set of books, government documents, technical reports, selected primary journal literature, and other online sources of information, with a goal of linking the HSDB content to as much publicly available information as possible. HSDB's content is peer-reviewed by the Scientific Review Panel, a group of experts in the areas covering the scope of HSDB content. Recent enhancements include the addition of chemical structures to HSDB records, the addition of new subfields such as age groups for human data, more occupational exposure standards, and the addition of information on numerous nanomaterials. Examples of future plans include providing more exposure-related information, e.g., uses of a chemical or substance in consumer products; the addition of information summaries aimed towards consumers and other members of the public wanting to learn about a chemical or substance; more visual content such as diagrams (images) of the pathways of metabolism of a substance; and enhanced search features and navigation.

Complementary and alternative medicine (CAM), such as acupuncture and herbal medicine, is popular in many countries. Yet, treatment outcomes of CAM are found to vary significantly between medical trials in different social environments. This paper addresses how the social organization of medicine affects medical treatment outcomes. In particular, it examines the extent to which two popular complementary and alternative medicine (CAM) interventions (acupuncture and herbal medicine) are coordinated with biomedicine and how coordination characteristics are related to the treatment outcomes of the two CAM interventions.

The impact and effectiveness of clinical trial data sharing initiatives may differ depending on the data sharing model used. We characterized outcomes associated with models previously used by the U.S. National Institutes of Health (NIH): National Heart, Lung, and Blood Institute's (NHLBI) centralized model and National Cancer Institute's (NCI) decentralized model. We identified trials completed in 2010-2013 that met NIH data sharing criteria and matched studies based on cost and/or size, determining whether trial data were shared, and for those that were, the frequency of secondary internal publications (authored by at least one author from the original research team) and shared data publications (authored by a team external to the original research team). We matched 77 NHLBI-funded trials to 77 NCI-funded trials; among these, 20 NHLBI-sponsored trials (26%) and 4 NCI-sponsored trials (5%) shared data (OR 6.4, 95% CI: 2.1, 19.8). From the 4 NCI-sponsored trials sharing data, we identified 65 secondary internal and 2 shared data publications. From the 20 NHLBI-sponsored trials sharing data, we identified 188 secondary internal and 53 shared data publications. The NHLBI's centralized data sharing model was associated with more trials sharing data and more shared data publications when compared with the NCI's decentralized model.

It is becoming increasingly common for individuals and organizations to use social media platforms such as Facebook. These are being used for a wide variety of purposes including disseminating, discussing and seeking health related information. U.S. Federal health agencies are leveraging these platforms to 'engage' social media users to read, spread, promote and encourage health related discussions. However, different agencies and their communications get varying levels of engagement. In this study we use statistical models to identify factors that associate with engagement.

Background: Healthcare costs are increasing in the U.S. Healthcare market is fragmented and opaque. The Amazon, JP Morgan Chase, and Berkshire Hathaway partnered to form an independent healthcare company 'Haven', designed to support cost-containment in health care and to forge a better patient experience. Limited information is available in the public domain about Haven's strategy to deliver cost-effective healthcare for their employees. Objective: To describe the impact of Haven Health of modern healthcare. Methods: We reviewed literature in Pubmed (MEDLINE database of references and abstracts on life sciences and biomedical topics from the USA National Library of Medicine at the National Institutes of Health) and the public domain. Results: Amazon's expertise and abilities in e-commerce such as logistics, supply, and big data management will support Haven's quest to resolve inefficiencies in health care. Haven may attempt to directly negotiate with providers, bypassing insurance companies, to establish themselves as an independent payor. Additionally, Haven to establish themselves as a provider by building new low-cost primary care clinics, focusing on chronic disease prevention. The new healthcare system may leverage machine learning, artificial intelligence and big data analysis to support its initiatives and other 'big data' analytics to drive it all. Conclusions: Heaven Health may use its expertise to disrupt everything from the pharmaceutical supply chain to primary care and telehealth. More research is needed to evaluate the impact of Haven Healthcare on disease outcomes and healthcare costs.

While the association between assets and depression has been established, less is known about the link between financial strain and depression. Given rising financial strain and economic inequity due to the COVID-19 pandemic, understanding the role that financial strain plays in shaping population depression in the United States is particularly salient. We conducted a scoping review of the peer-reviewed literature on financial strain and depression published from inception through January 19, 2023, in Embase, Medline via PubMed, and PsycINFO, PsycArticles, SocINDEX, and EconLit via Ebsco. We searched, reviewed, and synthesized the literature on longitudinal studies on financial strain and depression conducted in the United States. Four thousand and four unique citations were screened for eligibility. Fifty-eight longitudinal, quantitative articles on adults in the United States were included in the review. Eighty-three percent of articles (n = 48) reported a significant, positive association between financial strain and depression. Eight articles reported mixed results, featuring non-significant associations for some sub-groups and significant associations for others, one article was unclear, and one article reported no significant association between financial strain and depression. Five articles featured interventions to reduce depressive symptoms. Effective interventions included coping mechanisms to improve one's financial situation (e.g., mechanisms to assist in finding employment), to modify cognitive behavior (e.g., reframing mindset), and to engage support (e.g., engaging social and community support). Successful interventions were tailored to participants, were group-based (e.g., they included family members or other job seekers), and occurred over multiple sessions. While depression was defined consistently, financial strain was defined variably. Gaps in the literature included studies featuring Asian populations in the United States and interventions to reduce financial strain. There is a consistent, positive association between financial strain and depression in the United States. More research is needed to identify and test interventions that mitigate the ill effects of financial strain on population's mental health.

Dog ownership has been associated with reduced cardiovascular and all-cause mortality in civilian epidemiological samples. Associations between dog ownership and cardiometabolic disease were examined in the 2019-2020 wave of the National Health and Resilience in Veterans Study. Dog and cat ownership data were obtained from 3078 Veterans and cross-tabulated with self-reported, professionally diagnosed, heart disease, heart attack, stroke, high blood pressure, diabetes, and high cholesterol. In unadjusted tests, dog ownership was associated with lower rates of heart disease, high blood pressure, diabetes, and high cholesterol, while cat ownership was not. Relative to non-owners, dog owners were younger, were more likely to screen positive for posttraumatic stress disorder and/or major depressive disorder, and more active. Binary logistic regression models of associations between dog ownership and cardiometabolic disease were adjusted for age, sex, trauma load, mood disorder, substance abuse, nicotine abuse, and exercise. After adjustment, dog ownership was still associated with lower odds of hypertension and high cholesterol. Dog ownership also interacted with exercise to lower odds of heart disease and attenuated the effect of trauma load on hypertension. Conversely, age interacted with dog ownership such that odds of diabetes and stroke were higher in older Veterans who owned dogs.

Open Medicine celebrates its fifth year of publishing high quality academic work. This article looks at the achievements of the past five years and the challenges in the future.

The increasing importance of the Internet demands that toxicologists become aquainted with its resources. To find information, researchers must be able to effectively use Internet search engines, directories, subject-oriented websites, and library catalogs. The article will explain these resources, explore their benefits and weaknesses, and identify skills that help the researcher to improve search results and critically evaluate sources for their relevancy, validity, accuracy, and timeliness.

The COVID-19 pandemic poses extraordinary challenges to public health.

Information about personalized medicine abounds, yet it is difficult to comprehensively search for information on this topic due to the broadness of the term "personalized medicine," the variety of terms that are used to describe this concept, the vast amount of pertinent journal articles and Web sites, and the fast pace of developments in this field. A selected list of Web sites is provided as a starting place for information about concepts, terminology, projects, databases, tools, and stakeholders related to personalized medicine.

Chronic lymphocytic leukemia (CLL) is an adult lymphoid malignancy with a variable clinical course. There is considerable interest in the identification of new treatments, as most current approaches are not curative. While most patients respond to initial chemotherapy, relapsed disease is often resistant to the drugs commonly used in CLL and patients are left with limited therapeutic options. In this study, we used a luminescent cell viability assay based on ATP levels to find compounds that were potent and efficacious in killing CLL cells. We employed an in-house process of quantitative high throughput screening (qHTS) to assess 8 concentrations of each member of a 2,816 compound library (including FDA-approved drugs and those known to be bio-active from commercial suppliers). Using qHTS we generated potency values on each compound in lymphocytes donated from each of six individuals with CLL and five unaffected individuals. We found 102 compounds efficacious against cells from all six individuals with CLL ("consensus" drugs) with five of these showing low or no activity on lymphocytes from a majority of normal donors, suggesting some degree of specificity for the leukemic cells. To our knowledge, this is the first study to screen a drug library against primary CLL cells to identify candidate agents for anti-cancer therapy. The results presented here offer possibilities for the development of novel drug candidates for therapeutic uses to treat CLL and other diseases.

Development of a subunit vaccine targeting liver-stage Plasmodium parasites requires the identification of antigens capable of inducing protective T cell responses. However, traditional methods of antigen identification are incapable of evaluating T cell responses against large numbers of proteins expressed by these parasites. This bottleneck has limited development of subunit vaccines against Plasmodium and other complex intracellular pathogens. To address this bottleneck, we are developing a synthetic minigene technology for multi-antigen DNA vaccines. In an initial test of this approach, pools of long (150 bp) antigen-encoding oligonucleotides were synthesized and recombined into vectors by ligation-independent cloning to produce two DNA minigene library vaccines. Each vaccine encoded peptides derived from 36 (vaccine 1) and 53 (vaccine 2) secreted or transmembrane pre-erythrocytic P. yoelii proteins. BALB/cj mice were vaccinated three times with a single vaccine by biolistic particle delivery (gene gun) and screened for interferon-γ-producing T cell responses by ELISPOT. Library vaccination induced responses against four novel antigens. Naïve mice exposed to radiation-attenuated sporozoites mounted a response against only one of the four novel targets (PyMDH, malate dehydrogenase). The response to PyMDH could not be recalled by additional homologous sporozoite immunizations but could be partially recalled by heterologous cross-species sporozoite exposure. Vaccination against the dominant PyMDH epitope by DNA priming and recombinant Listeria boosting did not protect against sporozoite challenge. Improvements in library design and delivery, combined with methods promoting an increase in screening sensitivity, may enable complex minigene screening to serve as a high-throughput system for discovery of novel T cell antigens.

Structural and cultural barriers have led to limited access to and use of mental health services among immigrants in the United States (U.S.). This study provided a systematic review of factors associated with help-seeking attitudes, intentions, and behaviors among immigrants who are living in the U.S. This systematic review was performed using Medline, CINAHL, APA PsycInfo, Global Health, and Web of Science. Qualitative and quantitative studies examining mental help-seeking among immigrants in the U.S. were included. 954 records were identified through a search of databases. After removing duplicates and screening by title and abstract, a total of 104 articles were eligible for full-text review and a total of 19 studies were included. Immigrants are more reluctant to seek help from professional mental health services due to barriers such as stigma, cultural beliefs, lack of English language proficiency, and lack of trust in health care providers.

Library preparation is a key step in sequencing. For RNA sequencing there are advantages to both strand specificity and working with minute starting material, yet until recently there was no kit available enabling both. The Illumina TruSeq stranded mRNA Sample Preparation kit (TruSeq) requires abundant starting material while the Takara Bio SMART-Seq v4 Ultra Low Input RNA kit (V4) sacrifices strand specificity. The SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Pico) by Takara Bio claims to overcome these limitations. Comparative evaluation of these kits is important for selecting the appropriate protocol. We compared the three kits in a realistic differential expression analysis. We prepared and sequenced samples from two experimental conditions of biological interest with each of the three kits. We report differences between the kits at the level of differential gene expression; for example, the Pico kit results in 55% fewer differentially expressed genes than TruSeq. Nevertheless, the agreement of the observed enriched pathways suggests that comparable functional results can be obtained. In summary we conclude that the Pico kit sufficiently reproduces the results of the other kits at the level of pathway analysis while providing a combination of options that is not available in the other kits.

Antibody phage display is a key technology for the discovery and development of target-specific monoclonal antibodies (mAbs) for use in research, diagnostics, and therapy. The construction of a high-quality antibody library, with larger and more diverse antibody repertoires, is essential for the successful development of phage display-derived mAbs. In this study, a large human combinatorial single-chain variable fragment library (1.5 × 1011 colonies) was constructed from Epstein-Barr virus-infected human peripheral blood mononuclear cells stimulated with a combination of two of the activators of human B cells, the Toll-like receptor 7/8 agonist R848 and interleukin-2. Next-generation sequencing analysis with approximately 1.9 × 106 and 2.7 × 106 full-length sequences of heavy chain variable (VH) and κ light chain variable (Vκ) domains, respectively, revealed that the library consists of unique VH (approximately 94%) and Vκ (approximately 91%) sequences with greater diversity than germline sequences. Lastly, multiple unique mAbs with high affinity and broad cross-species reactivity could be isolated from the library against two therapeutically relevant target antigens, validating the library quality. These findings suggest that the novel antibody library we have developed may be useful for the rapid development of target-specific phage display-derived recombinant human mAbs for use in therapeutic and diagnostic applications.

Over the last nearly three decades in vitro display technologies have played an important role in the discovery and optimization of antibodies and other proteins for therapeutic applications. Here we describe the use of retroviral expression technology for the display of full-length IgG on B lineage cells in vitro with a hallmark of a tight and stable genotype to phenotype coupling. We describe the creation of a high-diversity (>1.0E09 different heavy- and light-chain combinations) cell displayed fully human antibody library from healthy donor-derived heavy- and light-chain gene libraries, and demonstrate the recovery of high affinity target-specific antibodies from this library by staining of cells with a labeled target antigen and their magnetic- and flow cytometry-based cell sorting. The present technology represents a further evolution in the discovery of full-length, fully human antibodies using mammalian display, and is termed Retrocyte Display® (Retroviral B lymphocyte Display).