In 2008 the National Institutes of Health established the Research, Condition and Disease Categorization Database (RCDC) that reports the amount spent by NIH institutes for each disease. Its goal is ...to allow the public "to know how the NIH spends their tax dollars," but it has been little used. The RCDC for 2018 was used to assess 428 schizophrenia-related research projects funded by the National Institute of Mental Health. Three senior psychiatrists independently rated each on its likelihood ("likely", "possible", "very unlikely") of improving the symptoms and/or quality of life for individuals with schizophrenia within 20 years. At least one reviewer rated 386 (90%), and all three reviewers rated 302 (71%), of the research projects as very unlikely to provide clinical improvement within 20 years. Reviewer agreement for the "very unlikely" category was good; for the "possible" category was intermediate; and for the "likely" category was poor. At least one reviewer rated 30 (7%) of the research projects as likely to provide clinical improvement within 20 years. The cost of the 30 projects was 5.5% of the total NIMH schizophrenia-related portfolio or 0.6% of the total NIMH budget. Study results confirm previous 2016 criticisms that the NIMH schizophrenia-related research portfolio disproportionately underfunds clinical research that might help people currently affected. Although the results are preliminary, since the RCDC database has not previously been used in this manner and because of the subjective nature of the assessment, the database would appear to be a useful tool for disease advocates who wish to ascertain how NIH spends its public funds.
It has been claimed that the National Institute of Mental Health (NIMH) budget, which traditionally has been evenly balanced between basic and clinical research, has shifted sharply and that 90% of ...NIMH resources are funding basic research. The authors used public data sources to assess this claim: the Research Condition and Disease Categorization Database, ClinicalTrials.gov, and the NIMH Strategic Plan for Research for 2020–2024. From 2016 to 2019, NIMH expenditures on bipolar disorder research decreased 25%, and those for schizophrenia research decreased 17.5%. From 2003 to 2019, NIMH support for treatment trials for schizophrenia, bipolar disorder, and major depressive disorder decreased 90%. NIMH’s Strategic Plan for Research for 2020–2024 suggests that the shift toward basic research will continue. Because NIMH’s primary purpose is to develop better treatments for current patients as well as future ones, the authors recommend that the ratio of basic to clinical research be readjusted to approximately 50:50.
The NIMH Research Portfolio: An Update Torrey, E Fuller; Simmons, Wendy W; Dailey, Lisa
Primary care companion for CNS disorders,
2023-Aug-01, Volume:
25, Issue:
4
Journal Article
Peer reviewed
To examine the funding priorities of the National Institute of Mental Health (NIMH) since 2016 to assess whether NIMH was continuing to prioritize basic research at the expense of clinical research.
...Six psychiatric disorders (schizophrenia, bipolar disorder, depression, anxiety disorders, eating disorders, autism) were assessed using 2 publicly available data sources (ClinicalTrials.gov and the National Institutes of Health Research, Condition, and Disease Categorization RCDC) to determine the degree of NIMH support for drug trials and research on these disorders in general since 2016.
From 2017 through 2022, ClinicalTrials.gov lists just 1 drug trial each for schizophrenia and bipolar disorder. The RCDC database for 2016 through 2021 shows that NIMH support for research projects on schizophrenia and bipolar disorder decreased by 22% and 20%, respectively. During that time, Congress increased the budget of NIMH by 40%.
NIMH has continued to prioritize basic research over clinical trials, resulting in a steep decline in funding for possible treatments for the most serious and costly psychiatric diseases.
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BACKGROUND:Baltimore, Philadelphia, and Washington, DC are geographically proximate cities with high HIV prevalence, including among black men who have sex with men (BMSM). Using data collected among ...BMSM in CDCʼs National HIV Behavioral Surveillance project, we compared socio-demographic characteristics, HIV risk behaviors, and service utilization to explore similarities and differences that could inform local and regional HIV intervention approaches.
METHODS:BMSM were recruited through venue time location sampling, June–December, 2011. Participants completed identical socio-behavioral surveys and voluntary HIV testing. Analyses were conducted among the full sample and those aged 18–24.
FINDINGS:Participants included 159 (DC), 364 (Baltimore), and 331 (Philadelphia) eligible BMSM. HIV prevalence was 23.1% (DC), 48.0% (Baltimore), 14.6% (Philadelphia) with 30.6%, 69.0%, 33.3% unrecognized HIV infection, respectively. Among BMSM 18–24, HIV prevalence was 11.1% (DC), 38.9% (Baltimore), 9.6% (Philadelphia) with unrecognized HIV infection 0.0%, 73.8%, 60.0% respectively. Compared with the other 2 cities, Baltimore participants were less likely to identify as gay/homosexual; more likely to report unemployment, incarceration, homelessness, sex exchange; and least likely to use the internet for partners. DC participants were more likely to have a college degree and employment. Philadelphia participants were more likely to report gay/homosexual identity, receptive condomless anal sex, having only main partners, and bars/clubs as partner meeting places. Sexually transmitted disease testing was universally low.
CONCLUSIONS:Analyses showed especially high HIV prevalence among BMSM in Baltimore including among young BMSM. Socio-demographic characteristics and HIV infection correlates differed across cities but unrecognized HIV infection and unknown partner status were universally high.
Biofilm formation is a harmful phenomenon in many areas, such as in industry and clinically, but offers advantages in the field of biocatalysis for the generation of robust biocatalytic platforms. In ...this work, we optimised growth conditions for the production of
Escherichia coli
biofilms by three strains (PHL644, a K-12 derivative with enhanced expression of the adhesin curli; the commercially-used strain BL21; and the probiotic Nissle 1917) on a variety of surfaces (plastics, stainless steel and PTFE).
E. coli
PHL644 and PTFE were chosen as optimal strain and substratum, respectively, and conditions (including medium, temperature, and glucose concentration) for biofilm growth were determined. Finally, the impact of these growth conditions on expression of the curli genes was determined using flow cytometry for planktonic and sedimented cells. We reveal new insights into the formation of biofilms and expression of curli in
E. coli
K-12 in response to environmental conditions.
The goal of the NIH Science of Behavior Change (SOBC) Common Fund Program is to provide the basis for an experimental medicine approach to behavior change that focuses on identifying and measuring ...the mechanisms that underlie behavioral patterns we are trying to change. This paper frames the development of the program within a discussion of the substantial disease burden in the U.S. attributable to behavioral factors, and details our strategies for breaking down the disease- and condition-focused silos in the behavior change field to accelerate discovery and translation. These principles serve as the foundation for our vision for a unified science of behavior change at the NIH and in the broader research community.
•Poor health behaviors account for a substantial proportion of disease burden in the U.S.•Behavior change is powerful at addressing this challenge, but it is difficult to get people to initiate and sustain desired behavioral change.•Scientific silos and a lack of focus on mechanisms of change have hindered progress in the behavior change field.•Precisely identifying mechanistic targets and adopting the experimental medicine approach can unify and advance the field.
Polymers are used routinely for equipment and infrastructure in hydrogen vehicle refueling stations, but significant gaps remain in understanding their hydrogen compatibility. The tribological ...properties of these materials in a high-pressure hydrogen environment is important in preventing component failure and the need for frequent replacement. We present in situ tribological studies on model rubbers, which include common fillers and plasticizer, using an in situ tribometer developed previously. Results suggest a clear, yet complicated, combined effect of the high-pressure hydrogen and the additives on the tribological performance of the chosen materials, as compared to matching experiments performed in ambient air. We find that the additives improved wear resistance in EPDM but deteriorated that in NBR due to disparate additive-polymer interactions.
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•Model rubbers are tribologically studied in situ under 27.6 MPa H2.•Friction increases for all model rubbers in the 27.6 MPa H2 environment.•Plasticizer results in reduced wear in high pressure H2 due to lubricating effects.•H2 affects plasticizer-rubber interactions in NBR to allow phase separation.•Wear performance depends in part on filler dispersion/distribution in the material.
The rate of adherence to regular colonoscopy screening in individuals at increased familial risk of colorectal cancer (CRC) is suboptimal, especially among rural and other geographically underserved ...populations. Remote interventions may overcome geographic and system-level barriers. We compared the efficacy of a telehealth-based personalized risk assessment and communication intervention with a mailed educational brochure for improving colonoscopy screening among at-risk relatives of patients with CRC.
Eligible individuals age 30 to 74 years who were not up-to-date with risk-appropriate screening and were not candidates for genetic testing were recruited after contacting patients with CRC or their next of kin in five states. Enrollees were randomly assigned as family units to either an active, personalized intervention that incorporated evidence-based risk communication and behavior change techniques, or a mailed educational brochure. The primary outcome was medically verified colonoscopy within 9 months of the intervention.
Of the 481 eligible and randomly assigned at-risk relatives, 79.8% completed the outcome assessments within 9 months; 35.4% of those in the personalized intervention group and 15.7% of those in the comparison group obtained a colonoscopy. In an intent-to-treat analysis, the telehealth group was almost three times as likely to get screened as the low-intensity comparison group (odds ratio, 2.83; 95% CI, 1.87 to 4.28; P < .001). Persons residing in rural areas and those with lower incomes benefitted at the same level as did urban residents.
Remote personalized interventions that consider family history and incorporate evidence-based risk communication and behavior change strategies may promote risk-appropriate screening in close relatives of patients with CRC.
Genetic and molecular studies suggest that activin receptor-like kinase 1 (ALK1) plays an important role in vascular development, remodeling, and pathologic angiogenesis. Here we investigated the ...role of ALK1 in angiogenesis in the context of common proangiogenic factors PAF; VEGF-A and basic fibroblast growth factor (bFGF). We observed that PAFs stimulated ALK1-mediated signaling, including Smad1/5/8 phosphorylation, nuclear translocation and Id-1 expression, cell spreading, and tubulogenesis of endothelial cells (EC). An antibody specifically targeting ALK1 (anti-ALK1) markedly inhibited these events. In mice, anti-ALK1 suppressed Matrigel angiogenesis stimulated by PAFs and inhibited xenograft tumor growth by attenuating both blood and lymphatic vessel angiogenesis. In a human melanoma model with acquired resistance to a VEGF receptor kinase inhibitor, anti-ALK1 also delayed tumor growth and disturbed vascular normalization associated with VEGF receptor inhibition. In a human/mouse chimera tumor model, targeting human ALK1 decreased human vessel density and improved antitumor efficacy when combined with bevacizumab (anti-VEGF). Antiangiogenesis and antitumor efficacy were associated with disrupted co-localization of ECs with desmin(+) perivascular cells, and reduction of blood flow primarily in large/mature vessels as assessed by contrast-enhanced ultrasonography. Thus, ALK1 may play a role in stabilizing angiogenic vessels and contribute to resistance to anti-VEGF therapies. Given our observation of its expression in the vasculature of many human tumor types and in circulating ECs from patients with advanced cancers, ALK1 blockade may represent an effective therapeutic opportunity complementary to the current antiangiogenic modalities in the clinic.
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting ...tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared with single agents. In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared with single agents. Mice bearing plasma cell tumors lived an average of 70 days longer on combination treatment compared with single agents. A set of 37 genes cooperatively affected (34 downregulated; 3 upregulated) by the combination responded pharmacodynamically in human myeloma cell lines, xenografts, and a P493 model, and were both enriched in tumors, and correlated with prognostic markers in myeloma patient datasets. Genes downregulated by the combination were overexpressed in several untreated cancers (breast, lung, colon, sarcoma, head and neck, myeloma) compared with normal tissues. The MYC/E2F axis, identified by upstream regulator analyses and validated by immunoblots, was significantly inhibited by the drug combination in several myeloma cell lines. Furthermore, 88% of the 34 genes downregulated have MYC-binding sites in their promoters, and the drug combination cooperatively reduced MYC half-life by 55% and increased degradation. Cells with MYC mutations were refractory to the combination. Thus, integrative approaches to understand drug synergy identified a clinically actionable strategy to inhibit MYC/E2F activity and tumor cell growth
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