Immunotherapy for leptomeningeal disease from solid tumors: current clinical outcomes and future opportunities.

Leptomeningeal disease is a debilitating, late-stage form of metastatic cancer disseminated within the cerebrospinal fluid, subarachnoid space, and leptomeninges, leading to significant neurological morbidity and mortality. As systemic cancer treatments improve, rates of leptomeningeal disease have increased, yet prognosis remains exceedingly poor. A wide range of treatment modalities have been trialed; however, no standard of care has been established.

A longitudinal study of queen health in honey bees reveals tissue specific response to seasonal changes and pathogen pressure.

The health of honey bee queens is crucial for colony success, particularly during stressful periods like overwintering. To accompany a previous longitudinal study of colony and worker health, we explored niche-specific gut microbiota, host gene expression, and pathogen prevalence in honey bee queens overwintering in a warm southern climate. We found differential gene expression and bacterial abundance with respect to various pathogens throughout the season.

A longitudinal field study of commercial honey bees shows that non-native probiotics do not rescue antibiotic treatment, and are generally not beneficial.

Probiotics are widely used in agriculture including commercial beekeeping, but there is little evidence supporting their effectiveness. Antibiotic treatments can greatly distort the gut microbiome, reducing its protective abilities and facilitating the growth of antibiotic resistant pathogens. Commercial beekeepers regularly apply antibiotics to combat bacterial infections, often followed by an application of non-native probiotics advertised to ease the impact of antibiotic-induced gut dysbiosis.

The Phenotype of a Bone Marrow Transplant Nurse: Survival of the Fittest.

There is a need for proficient nursing practice in specialized critical care settings, such as a pediatric Bone Marrow Transplant (BMT) Unit. The staffing crisis continues to be problematic for areas around the country. Nursing tenure has been positively correlated with improving patient outcomes and confidence in giving care, so efforts must be made to retain pediatric BMT nurses.

Alpha globin gene copy number and incident ischemic stroke risk among Black Americans.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( deletion would be associated with reduced risk of incident ischemic stroke.

Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

ART714 is a best-in-class antileukemic 2-carbon-linked dimeric artemisinin derivative.

Purpose: It has become increasingly clear that new multiagent combination regimens are required to improve survival rates in acute myeloid leukemia (AML). We recently reported that ART631, a first-in-class 2-carbon-linked artemisinin-derived dimer (2C-ART), was not only efficacious as a component of a novel three-drug combination regimen to treat AML, but, like other synthetic artemisinin derivatives, demonstrated low clinical toxicity. However, we ultimately found ART631 to have suboptimal solubility and stability properties, thus limiting its potential for clinical development.

Alpha globin gene copy number and incident ischemic stroke risk among Black Americans.

Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( deletion would be associated with reduced risk of incident ischemic stroke.

Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

Ecology of Pollen Storage in Honey Bees: Sugar Tolerant Yeast and the Aerobic Social Microbiota.

Honey bee colonies are resource rich and densely populated, generating a constant battle to control microbial growth. Honey is relatively sterile in comparison with beebread: a food storage medium comprising pollen mixed with honey and worker head-gland secretions. Within colonies, the microbes that dominate aerobic niches are abundant throughout social resource space including stored pollen, honey, royal jelly, and the anterior gut segments and mouthparts of both queens and workers.

A high-throughput sequencing survey characterizing European foulbrood disease and Varroosis in honey bees.

As essential pollinators of ecosystems and agriculture, honey bees (Apis mellifera) are host to a variety of pathogens that result in colony loss. Two highly prevalent larval diseases are European foulbrood (EFB) attributed to the bacterium Melissococcus plutonius, and Varroosis wherein larvae can be afflicted by one or more paralytic viruses. Here we used high-throughput sequencing and qPCR to detail microbial succession of larval development from six diseased, and one disease-free apiary.

Changes in gut microbiota and metabolism associated with phenotypic plasticity in the honey bee .

Honey bees exhibit an elaborate social structure based in part on an age-related division of labor. Young workers perform tasks inside the hive, while older workers forage outside the hive, tasks associated with distinct diets and metabolism. Critical to colony fitness, the work force can respond rapidly to changes in the environment or colony demography and assume emergency tasks, resulting in young foragers or old nurses.

"What's Important to You, Max?": The Influence of Goals on Engagement in an Interactive Narrative for Adolescent Health Behavior Change.

Interactive narrative technologies for preventive health care offer significant potential for promoting health behavior change in adolescents. By improving adolescents' knowledge, personal efficacy, and self-regulatory skills these technologies hold great promise for realizing positive impacts on adolescent health. These potential benefits are enabled through story-centric learning experiences that provide opportunities for adolescents to practice strategies to reduce risky health behaviors in engaging game-based environments.

A pragmatic strength and conditioning intervention for firefighters: Feasibility of the Tactical Athlete Resilience Program (TARP).

Issue Addressed: Firefighting is physically and mentally taxing and recruits are expected to have optimal health and fitness. However, physical fitness tends to decline following initial training, placing firefighters at an increased risk for stress and injury. Efforts are needed to engage and support firefighters in maintaining adequate health and fitness to withstand the rigorous demands of their occupation.

Early Queen Development in Honey Bees: Social Context and Queen Breeder Source Affect Gut Microbiota and Associated Metabolism.

The highly social honey bee has dense populations but a significantly reduced repertoire of immune genes relative to solitary species, suggesting a greater reliance on social immunity. Here we investigate immune gene expression and gut microbial succession in queens during colony introduction. Recently mated queens were placed into an active colony or a storage hive for multiple queens: a queen-bank.

Alpha globin gene copy number and hypertension risk among Black Americans.

Background: Alpha globin is expressed in the endothelial cells of human resistance arteries where it binds to endothelial nitric oxide synthase and limits release of the vasodilator nitric oxide. Genomic deletion of the alpha globin gene (HBA) is common among Black Americans and could lead to increased endothelial nitric oxide signaling and reduced risk of hypertension.

Methods: Community-dwelling US adults aged 45 years or older were enrolled and examined from 2003 to 2007, followed by telephone every 6 months, and reexamined from 2013 to 2016.

Social Interaction is Unnecessary for Hindgut Microbiome Transmission in Honey Bees: The Effect of Diet and Social Exposure on Tissue-Specific Microbiome Assembly.

Honey bees are a model for host-microbial interactions with experimental designs evolving towards conventionalized worker bees. Research on gut microbiome transmission and assembly has examined only a fraction of factors associated with the colony and hive environment. Here, we studied the effects of diet and social isolation on tissue-specific bacterial and fungal colonization of the midgut and two key hindgut regions.

Targeting oncometabolism to maximize immunotherapy in malignant brain tumors.

Brain tumors result in significant morbidity and mortality in both children and adults. Recent data indicate that immunotherapies may offer a survival benefit after standard of care has failed for malignant brain tumors. Modest results from several late phase clinical trials, however, underscore the need for more refined, comprehensive strategies that incorporate new mechanistic and pharmacologic knowledge.

A Novel 2-Carbon-Linked Dimeric Artemisinin With Potent Antileukemic Activity and Favorable Pharmacology.

Acute myeloid leukemia (AML) remains a devastating disease, with low cure rates despite intensive standard chemotherapy regimens. In the past decade, targeted antileukemic drugs have emerged from research efforts. Nevertheless, targeted therapies are often effective for only a subset of patients whose leukemias harbor a distinct mutational or gene expression profile and provide only transient antileukemic responses as monotherapies.

Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans.

Background: -Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances -adrenergic-mediated vasoconstriction. -Globin gene ( copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that copy number would be associated with kidney disease risk.

Optimization of ether and aniline based inhibitors of lactate dehydrogenase.

Lactate dehydrogenase (LDH) is a critical enzyme in the glycolytic metabolism pathway that is used by many tumor cells. Inhibitors of LDH may be expected to inhibit the metabolic processes in cancer cells and thus selectively delay or inhibit growth in transformed versus normal cells. We have previously disclosed a pyrazole-based series of potent LDH inhibitors with long residence times on the enzyme.

Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.

Artemisinins are active against human leukemia cell lines and have low clinical toxicity in worldwide use as antimalarials. Because multiagent combination regimens are necessary to cure fully evolved leukemias, we sought to leverage our previous finding that artemisinin analogs synergize with kinase inhibitors, including sorafenib (SOR), by identifying additional synergistic antileukemic drugs with low toxicity. Screening of a targeted antineoplastic drug library revealed that B-cell lymphoma 2 (BCL2) inhibitors synergize with artemisinins, and validation assays confirmed that the selective BCL2 inhibitor, venetoclax (VEN), synergized with artemisinin analogs to inhibit growth and induce apoptotic cell death of multiple acute leukemia cell lines in vitro.

Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites.

The spread of Plasmodium falciparum parasites resistant to most first-line antimalarials creates an imperative to enrich the drug discovery pipeline, preferably with curative compounds that can also act prophylactically. We report a phenotypic quantitative high-throughput screen (qHTS), based on concentration-response curves, which was designed to identify compounds active against Plasmodium liver and asexual blood stage parasites. Our qHTS screened over 450,000 compounds, tested across a range of 5 to 11 concentrations, for activity against Plasmodium falciparum asexual blood stages.

Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties.

Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate, with concomitant oxidation of reduced nicotinamide adenine dinucleotide as the final step in the glycolytic pathway. Glycolysis plays an important role in the metabolic plasticity of cancer cells and has long been recognized as a potential therapeutic target. Thus, potent, selective inhibitors of LDH represent an attractive therapeutic approach.

Microbial Ecology of European Foul Brood Disease in the Honey Bee (): Towards a Microbiome Understanding of Disease Susceptibility.

European honey bees ( Linnaeus) are beneficial insects that provide essential pollination services for agriculture and ecosystems worldwide. Modern commercial beekeeping is plagued by a variety of pathogenic and environmental stressors often confounding attempts to understand colony loss. European foulbrood (EFB) is considered a larval-specific disease whose causative agent, , has received limited attention due to methodological challenges in the field and laboratory.

Propolis Envelope Promotes Beneficial Bacteria in the Honey Bee () Mouthpart Microbiome.

Honey bees collect and apply plant resins to the interior of their nest cavity, in order to form a layer around the nest cavity called a propolis envelope. Propolis displays antimicrobial activity against honey bee pathogens, but the effect of propolis on the honey bee microbiome is unknown. Honey bees do not intentionally consume propolis, but they do manipulate propolis with their mouthparts.