Explore the vast range of titles available.

Maintaining the integrity of cryogenically preserved biological materials is critical, as even brief, undetected temperature excursions in storage can compromise sample viability. Existing monitoring systems may miss transient thaw–refreeze events, posing serious quality risks. To address this, we developed and validated frozen indicator tubes that visually signal deviations from the frozen state, serving as a cost-effective backup to electronic monitors. Our first method uses an aqueous dye solution that immobilizes the dye when frozen; any thawing causes the dye to disperse, providing a clear, external visual cue of a partial or complete thaw. For ultra-low-temperature storage (−80 °C), we introduced a second method using an ethanol-based solution calibrated to indicate thaw events. This system detects temperature rises of 10 °C or more sustained for at least fifteen minutes—conditions that may jeopardize sample stability. When paired with standard monitoring systems, these indicator tubes offer an added layer of protection by providing simple, reliable, and immediate visual confirmation of critical temperature breaches. This innovation enhances confidence in cryogenic storage protocols and supports the long-term preservation of sensitive biological materials.

Chromosome organization is crucial for genome function. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. Using the super-resolution microscopy methods of OligoSTORM and OligoDNA-PAINT, we trace 8 megabases of human chromosome 19, visualizing structures ranging in size from a few kilobases to over a megabase. Focusing on chromosomal regions that contribute to compartments, we discover distinct structures that, in spite of considerable variability, can predict whether such regions correspond to active (A-type) or inactive (B-type) compartments. Imaging through the depths of entire nuclei, we capture pairs of homologous regions in diploid cells, obtaining evidence that maternal and paternal homologous regions can be differentially organized. Finally, using restraint-based modeling to integrate imaging and Hi-C data, we implement a method-integrative modeling of genomic regions (IMGR)-to increase the genomic resolution of our traces to 10 kb.

Forests are increasingly threatened by climate-change-fuelled cycles of drought, dieback and wildfires. However, for reasons that remain incompletely understood, some forest stands are more vulnerable than others, leaving a patchwork of varying dieback and wildfire risk after drought. Here, we show that spatial variability in forest drought response can be explained by differences in underlying bedrock. Our analysis links geochemical measurements of bedrock composition, geophysical measurements of subsurface weathering and remotely sensed changes in evapotranspiration during the 2011–2017 drought in California. We find that evapotranspiration plummeted in dense forest stands rooted in weathered, nutrient-rich bedrock. By contrast, relatively unweathered, nutrient-poor bedrock supported thin forest stands that emerged unscathed from the drought. By influencing both subsurface weathering and nutrient supply, bedrock composition regulates the balance of water storage and demand in mountain ecosystems. However, rather than enhancing forest resilience to drought by providing more water-storage capacity, bedrock with more weatherable and nutrient-rich minerals induced greater vulnerability by enabling a boom–bust cycle in which higher ecosystem productivity during wet years drives excess plant water demand during droughts. Spatial variability in forest dieback during the severe drought in California between 2011 and 2017 can be explained by variations in bedrock composition and thus weatherability, according to analyses of the drought responses a series of geologically distinct sites.

A modular leadless pacemaker in wireless communication with a subcutaneous implantable cardioverter–defibrillator was shown to be safe and exceeded performance goals for communication between the pacemaker and ICD.

Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4–24.8 μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au/), ID: ACTRN12611001200976.

Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined leukemia stem cells, while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anticancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients. Mechanistic studies indicate that flavaglines strongly inhibit protein synthesis, leading to the reduction of short-lived antiapoptotic proteins. Notably though, treatment with flavaglines, alone or in combination with other drugs, yields a much stronger cytotoxic activity toward leukemia cells than the translational inhibitor temsirolimus. These results indicate that the underlying cell death mechanism of flavaglines is more complex than simply inhibiting general protein translation. Global gene expression profiling and cell biological assays identified Myc inhibition and the disruption of mitochondrial integrity to be features of flavaglines, which we propose contribute to their efficacy in targeting leukemia cells. Taken together, these findings indicate that rocaglamide and silvestrol are distinct from clinically available translational inhibitors and represent promising candidates for the treatment of leukemia.

Environmental health (EH) professionals, one of the largest segments of the public health workforce, are responsible for delivery of essential environmental public health services. The challenges facing these professionals and research needs to improve EH practice are not fully understood, but 26% of EH professionals working in health departments of the United States plan to retire in 5 y, while only 6% of public health students are currently pursuing EH concentrations. A groundbreaking initiative was recently launched to understand EH practice in health departments of the United States. This commentary article aims to identify priority EH practice challenges and related research needs for health departments. A horizon scanning approach was conducted in which challenges facing EH professionals were provided by 1,736 respondents working at health departments who responded to a web-based survey fielded in November 2017. Thematic analyses of the responses and determining the frequency at which respondents reported specific issues and opportunities identified primary EH topic areas. These topic areas and related issues informed focus group discussions at an in-person workshop held in Anaheim, California. The purpose of the in-person workshop was to engage each of the topic areas and issues, through facilitated focus groups, leading to the formation of four to five related problem statements for each EH topic. EH professionals are strategically positioned to diagnose, intervene, and prevent public health threats. Focus group engagement resulted in 29 priority problem statements partitioned among 6 EH topic areas: ) drinking water quality, ) wastewater management, ) healthy homes, ) food safety, ) vectors and public health pests, and ) emerging issues. This commentary article identifies priority challenges and related research needs to catalyze effective delivery of essential environmental public health services for common EH program areas in health departments. An unprecedented initiative to revitalize EH practice with timely and strategic recommendations for student and professional training, nontraditional partnerships, and basic and translational research activities is recommended. https://doi.org/10.1289/EHP5161.

A Reduced-Fat Diet and Aerobic Exercise in J apanese A mericans With Impaired Glucose Tolerance Decreases Intra-Abdominal Fat and Improves Insulin Sensitivity but not β-Cell Function Darcy B. Carr 1 , Kristina M. Utzschneider 2 , Edward J. Boyko 3 , Pamela J. Asberry 2 , Rebecca L. Hull 2 , Keiichi Kodama 2 , Holly S. Callahan 4 , Colleen C. Matthys 4 , Donna L. Leonetti 5 , Robert S. Schwartz 6 , Steven E. Kahn 2 and Wilfred Y. Fujimoto 2 1 Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 2 Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, Washington 3 Epidemiologic Research and Information Center and Department of Medicine, Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, Washington 4 General Clinical Research Center, Seattle, Washington 5 Department of Anthropology, University of Washington, Seattle, Washington 6 Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington Address correspondence and reprint requests to Darcy B. Carr, MD, Assistant Professor, Dept. of ObstetricsGynecology, Box 356460, University of Washington, Seattle, WA 98195-6460. E-mail: darcarr{at}u.washington.edu Abstract Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, β-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or β-cell function and to evaluate these effects over time, we quantified insulin sensitivity and the acute insulin response to glucose (AIRg) in 62 Japanese Americans (age 56.5 ± 1.3 years; mean ± SE) with impaired glucose tolerance (IGT) who were randomized to the American Heart Association (AHA) Step 2 diet plus endurance exercise ( n = 30) versus the AHA Step 1 diet plus stretching ( n = 32) for 24 months. β-Cell function (disposition index [DI]) was calculated as S i × AIRg, where S i is the insulin sensitivity index. The incremental area under the curve for glucose (incAUCg) was calculated from a 75-g oral glucose tolerance test. Intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were measured by computed tomography. At 24 months, the Step 2/endurance group had lower weight (63.1 ± 2.4 vs. 71.3 ± 2.9 kg; P = 0.004) and IAF (75.0 ± 7.9 vs. 112.7 ± 10.4 cm 2 ; P = 0.03) and SCF (196.5 ± 18.0 vs. 227.7 ± 19.9 cm 2 ; P < 0.001) areas, greater S i (4.7 ± 0.5 vs. 3.3 ± 0.3 × 10 −5 min · pmol −1 · l −1 ; P = 0.01), and a trend toward lower AIRg (294.9 ± 50.0 vs. 305.4 ± 30.0 pmol/l; P = 0.06) and incAUCg (8,217.3 ± 350.7 vs. 8,902.0 ± 367.2 mg · dl −1 · 2 h −1 ; P = 0.08) compared with the Step 1/stretching group after adjusting for baseline values. There was no difference in the DI ( P = 0.7) between the groups. S i was associated with changes in weight ( r = −0.426, P = 0.001) and IAF ( r = −0.395, P = 0.003) and SCF ( r = −0.341, P = 0.01) areas. Thus, the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT. However, such changes did not improve β-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term. AHA, American Heart Association AIRg, acute insulin response to glucose CT, computed tomography DI, disposition index DPP, Diabetes Prevention Program ESD, extreme studentized deviate FSIGTT, frequently sampled intravenous glucose tolerance test IAF, intra-abdominal fat IGT, impaired glucose tolerance OGTT, oral glucose tolerance test SCF, subcutaneous fat UKPDS, U.K. Prospective Diabetes Study Footnotes Accepted October 29, 2004. Received April 20, 2004. DIABETES

Significant progress has been made in radiation protection for children during the last 10 years. This includes increased awareness of the need for radiation protection for pediatric patients with international partnerships through the Alliance for Radiation Safety in Pediatric Imaging. This paper identifies five areas of significant progress in radiation safety for children: the growth of the Alliance; the development of an adult radiation protection campaign Image Wisely™; increased collaboration with government agencies, societies and the vendor community; the development of national guidelines in pediatric nuclear medicine, and the development of a size-based patient dose correction factor by the American Association of Physicists in Medicine, Task Group 204. However, many challenges remain. These include the need for continued education and change of practice at adult-focused hospitals where many pediatric CT exams are performed; the need for increased emphasis on appropriateness of pediatric imaging and outcomes research to validate the performance of CT studies, and the advancement of the work of the first pediatric national dose registry to determine the “state of the practice” with the final goal of establishing ranges of optimal CT technique for specific scan indications when imaging children with CT.