Optimizing Care for Military Women: The Value of the Dual-Certified Family and Women's Health Nurse Practitioner.

The number of women in the military has more than tripled over the past 50 years, increasing from 5% in the 1970s to 17% in 2023, making them essential for global health engagement and military operations. Provider competence and confidence are barriers to the consistent availability of preventive, gynecologic, and reproductive services for women across service locations and duty platforms. The Defense Health Board recommends standardizing services and improving the availability and scope of services for women at every point of care. In direct conflict with these recommendations, however, is a congressional call for a drawdown of medical forces, which creates a need for operationally trained clinicians with a broad skill set including comprehensive care for women. Advanced practice registered nurses, such as family and women's health nurse practitioners, are key assets to fill this gap on military medical health-care teams. At the request of the U.S. Air Force, the Graduate School of Nursing at the Uniformed Services University began offering a Women's Health Nurse Practitioner (WHNP) program in 2014. The WHNP curriculum was layered onto the existing Family Nurse Practitioner program so that Family Nurse Practitioner students receive enhanced education in women's health and WHNP students are prepared to meet the holistic, primary care needs of patients across the lifespan in addition to caring for women with obstetric and urogenital health concerns. This article highlights the value of dual-certified Family Nurse Practitioners and WHNPs in the military health-care system. These Uniformed Services University alumni are uniquely prepared to provide comprehensive primary and specialty care for female warfighters across the lifecycle from stable, well-resourced duty stations to austere, operational settings or deployment platforms.

Competition for pollinators destabilizes plant coexistence.

Mounting concern over the global decline of pollinators has fuelled calls for investigating their role in maintaining plant diversity1,2. Theory predicts that competition for pollinators can stabilize interactions between plant species by providing opportunities for niche differentiation3, while at the same time can drive competitive imbalances that favour exclusion4. Here we empirically tested these contrasting effects by manipulating competition for pollinators in a way that predicts its long-term implications for plant coexistence. We subjected annual plant individuals situated across experimentally imposed gradients in neighbour density to either ambient insect pollination or a pollen supplementation treatment alleviating competition for pollinators. The vital rates of these individuals informed plant population dynamic models predicting the key theoretical metrics of species coexistence. Competition for pollinators generally destabilized the interactions between plant species, reducing the proportion of pairs expected to coexist. Interactions with pollinators also influenced the competitive imbalances between plant species, effects that are expected to strengthen with pollinator decline, potentially disrupting plant coexistence. Indeed, results from an experiment simulating pollinator decline showed that plant species experiencing greater reductions in floral visitation also suffered greater declines in population growth rate. Our results reveal that competition for pollinators may weaken plant coexistence by destabilizing interactions and contributing to competitive imbalances, information critical for interpreting the impacts of pollinator decline.

Examining Factors Associated with Utilization of Chaplains in the Acute Care Setting.

Hospitalized persons want their spiritual needs addressed and discussed by the healthcare team, but medical providers and nurses lack the necessary training. Patients want chaplaincy care, but very few receive it, and little is known about utilization factors. To identify the population characteristics associated with the utilization of chaplaincy services, hospitalization data from March 2012 to July 2017 were analyzed (N = 15,242 patients). Religiously affiliated individuals and those with the most acute health needs were more likely to receive chaplaincy care and received more total care. Patient-centered healthcare models may need to evaluate strategic integration of spiritual care beyond reactive spiritual care provision.

Relative demographic susceptibility does not explain the extinction chronology of Sahul's megafauna.

The causes of Sahul's megafauna extinctions remain uncertain, although several interacting factors were likely responsible. To examine the relative support for hypotheses regarding plausible ecological mechanisms underlying these extinctions, we constructed the first stochastic, age-structured models for 13 extinct megafauna species from five functional/taxonomic groups, as well as 8 extant species within these groups for comparison. Perturbing specific demographic rates individually, we tested which species were more demographically susceptible to extinction, and then compared these relative sensitivities to the fossil-derived extinction chronology. Our models show that the macropodiformes were the least demographically susceptible to extinction, followed by carnivores, monotremes, vombatiform herbivores, and large birds. Five of the eight extant species were as or more susceptible than the extinct species. There was no clear relationship between extinction susceptibility and the extinction chronology for any perturbation scenario, while body mass and generation length explained much of the variation in relative risk. Our results reveal that the actual mechanisms leading to the observed extinction chronology were unlikely related to variation in demographic susceptibility per se, but were possibly driven instead by finer-scale variation in climate change and/or human prey choice and relative hunting success.

Carbonic anhydrase activity in the frontal lobe of human brain.

Carbonic anhydrase (CA) plays an important role in many biological processes. Recent technological advances have demonstrated the feasibility of measuring CA activity in the occipital lobe of human subjects in vivo. In this work we report, for the first time, in vivo measurement of CA activity in the frontal lobe of human brain, where structural and function abnormalities are strongly associated with symptoms of major psychiatric disorders. Despite the much larger magnetic field distortion in the frontal lobe, the pseudo first-order bicarbonate dehydration rate constant was determined with high precision using in vivo 13 C magnetic resonance magnetization transfer spectroscopy following oral administration of [U-13 C6 ]glucose. Nuclear Overhauser effect pulses were used to increase the signal-to-noise ratio; no proton decoupling was applied. The unidirectional dehydration rate constant of bicarbonate was found to be 0.26 ± 0.07 s-1 , which is not statistically different from the dehydration rate constant in the occipital lobe determined in our previous study, indicating that CA activity in the two brain regions is essentially indistinguishable. These results demonstrate the feasibility of characterizing CA activity in the frontal lobe for future psychiatric studies.

Cerebral phosphoester signals measured by 31P magnetic resonance spectroscopy at 3 and 7 Tesla.

Abnormal cell membrane metabolism is associated with many neuropsychiatric disorders. Free phosphomonoesters and phosphodiesters, which can be detected by in vivo 31P magnetic resonance spectroscopy (MRS), are important cell membrane building blocks. However, the quantification of phosphoesters has been highly controversial even in healthy individuals due to overlapping signals from macromolecule membrane phospholipids (MP). In this study, high signal-to-noise ratio (SNR) cerebral 31P MRS spectra were acquired from healthy volunteers at both 3 and 7 Tesla. Our results indicated that, with minimal spectral interference from MP, the [phosphocreatine (PCr)]/[phosphocholine (PC) + glycerophosphocholine (GPC)] ratio measured at 7 Tesla agreed with its value expected from biochemical constraints. In contrast, the 3 Tesla [PCr]/[PC+GPC] ratio obtained using standard spectral fitting procedures was markedly smaller than the 7 Tesla ratio and than the expected value. The analysis suggests that the commonly used spectral model for MP may fail to capture its complex spectral features at 3 Tesla, and that additional prior knowledge is necessary to reliably quantify the phosphoester signals at low magnetic field strengths when spectral overlapping is significant.

Optimizing screening and management of cardiovascular health in prostate cancer: A review.

In clinical practice, cancer management does not consistently encompass screening and identification of cardiovascular (CV) risk. The use of androgen deprivation therapy (ADT) in prostate cancer has been associated with increased CV risk and development of metabolic syndrome, necessitating identification of patients at risk in this population (e.g., those with pre-existing CV disease). A multidisciplinary team of Canadian physicians was assembled to develop a series of recommendations intended to identify patients who may benefit from optimal management of their CV disease and/or modification of cardiac risk factors. A key goal was the development of a simple screening tool for identification of patients with pre-existing CV disease. This simple and inclusive set of recommendations are intended for use within urology clinics to facilitate holistic approaches and simplify the management of patients.

The Contribution of Physician-System Integrating Structure to Select Health System Outcomes.

Physician groups are increasingly being vertically integrated with hospitals and health systems; yet, the evidence on the impact of physician-system integration on health system outcomes is mixed. The objective of this study was to examine the impact of increased physician-system integration on select health system outcomes. We used a mixed-methods approach: (1) a fixed-effects multivariate mediation analysis; and (2) a qualitative analysis of interviews with health executives (n = 25). Our findings showed that hospitals spent $633 375.22 to $827 110.24 for each "level" increase in integration. This relationship was attenuated, however, by the presence of care coordination mechanisms.

Fragment-to-Lead Medicinal Chemistry Publications in 2018.

This Perspective, the fourth in an annual series, summarizes fragment-to-lead (F2L) success stories published during 2018. Topics such as target class, screening methods, physicochemical properties, and ligand efficiency are discussed for the 2018 examples as well as for the combined 111 F2L examples covering 2015-2018. While the overall properties of fragments and leads have remained constant, a number of new trends are noted, for example, broadening of target class coverage and application of FBDD to covalent inhibitors. Moreover, several studies make use of fragment hits that were previously described in the literature, illustrating that fragments are versatile starting points that can be optimized to structurally diverse leads. By focusing on success stories, the hope is that this Perspective will identify and inform best practices in fragment-based drug discovery.

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss.

Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure.

Maneuvering Clinical Pathways for Ulcerative Colitis.

PURPOSE OF REVIEW: Recent years have brought about several advances in the treatment of patients with ulcerative colitis (UC). Here, we discuss salient recommendations of recent treatment guidelines; review the efficacy, safety, and real-world data of vedolizumab and tofacitinib; appraise their place vis-à-vis established agents; and consider the newly proposed approaches of risk-stratified and treat-to-target therapy. RECENT FINDINGS: Once daily oral mesalamine dosing is equivalent to split dosing in mild-moderate UC. Real-world data are accumulating on the effectiveness and safety of vedolizumab for moderate to severe UC, while there are few such data on the most recently approved agent, tofacitinib. High-dose infliximab is being investigated for severe UC. New approaches are challenging the established paradigm of selecting therapy based on current disease activity. The risk-stratified approach incorporates long-term risk as well as the current burden of inflammation. The treat-to-target approach aims at improved long-term outcomes by adjusting therapy to resolve intestinal inflammation. The therapeutic options for UC are continually expanding. Risk-stratified therapy and the treat-to-target approach represent paradigm shifts in UC management. Optimal disease control requires an individualized approach that takes into consideration current inflammatory burden, long-term risk, patient preferences, and ongoing assessment of response to treatment.

Quantification of in vivo transverse relaxation of glutamate in the frontal cortex of human brain by radio frequency pulse-driven longitudinal steady state.

PURPOSE: The principal excitatory neurotransmitter glutamate plays an important role in many central nervous system disorders. Because glutamate resides predominantly in glutamatergic neurons, its relaxation properties reflect the intracellular environment of glutamatergic neurons. This study developed an improved echo time-independent technique for measuring transverse relaxation time and demonstrated that this radio frequency (RF)-driven longitudinal steady state technique can reliably measure glutamate transverse relaxation in the frontal cortex, where structural and functional abnormalities have been associated with psychiatric symptoms. METHOD: Bloch and Monte Carlo simulations were performed to improve and optimize the RF-driven, longitudinal, steady-state (MARzss) technique to significantly shorten scan time and increase measurement precision. Optimized four-flip angle measurements at 0°,12°, 24°, and 36° with matched repetition time were used in nine human subjects (6F, 3M; 27-49 years old) at 7 Tesla. Longitudinal and transverse relaxation rates for glutamate were measured from a 2 x 2 x 2 cm3 voxel placed in three different brain regions: gray matter-dominated medial prefrontal lobe, white matter-dominated left frontal lobe, and gray matter-dominated occipital lobe. RESULTS: Compared to the original MARzss technique, the scan time per voxel for measuring glutamate transverse relaxation was shortened by more than 50%. In the medial frontal, left frontal, and occipital voxels, the glutamate T2 was found to be 117.5±12.9 ms (mean ± standard deviation, n = 9), 107.3±12.1 (n = 9), and 124.4±16.6 ms (n = 8), respectively. CONCLUSIONS: The improvements described in this study make the MARZSS technique a viable tool for reliably measuring glutamate relaxation from human subjects in a typical clinical setting. It is expected that this improved technique can be applied to characterize the intracellular environment of glutamatergic neurons in a variety of brain disorders.

Fragment-to-Lead Medicinal Chemistry Publications in 2017.

This Miniperspective is the third in a series reviewing fragment-to-lead publications from a given year. Following our reviews for 2015 and 2016, this Miniperspective provides tabulated summaries of relevant articles published in 2017 along with some general observations. In addition, we discuss insights obtained from analysis of the combined data set of 85 examples from all three years of publications.

Injectable, Magnetically Orienting Electrospun Fiber Conduits for Neuron Guidance.

Magnetic electrospun fibers are of interest for minimally invasive biomaterial applications that also strive to provide cell guidance. Magnetic electrospun fibers can be injected and then magnetically positioned in situ, and the aligned fiber scaffolds provide consistent topographical guidance to cells. In this study, magnetically responsive aligned poly-l-lactic acid electrospun fiber scaffolds were developed and tested for neural applications. Incorporating oleic acid-coated iron oxide nanoparticles significantly increased neurite outgrowth, reduced the fiber alignment, and increased the surface nanotopography of the electrospun fibers. After verifying neuron viability on two-dimensional scaffolds, the system was tested as an injectable three-dimensional scaffold. Small conduits of aligned magnetic fibers were easily injected in a collagen or fibrinogen hydrogel solution and repositioned using an external magnetic field. The aligned magnetic fibers provided internal directional guidance to neurites within a three-dimensional collagen or fibrin model hydrogel, supplemented with Matrigel. Neurites growing from dorsal root ganglion explants extended 1.4-3× farther on the aligned fibers compared with neurites extending in the hydrogel alone. Overall, these results show that magnetic electrospun fiber scaffolds can be injected and manipulated with a magnetic field in situ to provide directional guidance to neurons inside an injectable hydrogel. Most importantly, this injectable guidance system increased both neurite alignment and neurite length within the hydrogel scaffold.

Assessments of Temporal Variations in Haplotypes of 'Candidatus Liberibacter solanacearum' and Its Vector, the Potato Psyllid, in Potato Fields and Native Vegetation.

The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), had been known for nearly a century to cause psyllid yellows of solanaceous crops. However, it has only been a decade since the insect was discovered to transmit the bacterium 'Candidatus Liberibacter solanacearum' (Lso), which putatively causes potato zebra chip disease. This project was initiated to quantify temporal incidences of haplotypes of the psyllid (Central, Southwestern, and Western) and Lso (A, B) in potato fields and in native vegetation. Psyllids were collected from native vegetation in Texas (2011-2014), and from potato fields in Texas and New Mexico (2014-2017). Psyllids were tested for Lso and haplotypes of both psyllid and Lso. In Texas, the Central psyllid haplotype was overwhelmingly dominant both in potato fields and in native vegetation regardless of location and time of collection. However, in New Mexico potato fields, although the Southwestern haplotype was overall dominant, the ratios of individual haplotypes varied among years and within a season. The Southwestern psyllid haplotype was greater in incidence than the Central early but declined later in the season in each of the 4 yr, while the Central haplotype was low in incidence early but increased over time. Lso was detected in all three psyllid haplotypes representing the first report in Southwestern psyllid haplotype. In Texas, Lso haplotype A was more frequently detected than B, but in New Mexico the incidence of positive psyllids was not high enough to make definitive conclusions regarding predominant Lso haplotype.

Fold stability during endolysosomal acidification is a key factor for allergenicity and immunogenicity of the major birch pollen allergen.

BACKGROUND: The search for intrinsic factors, which account for a protein's capability to act as an allergen, is ongoing. Fold stability has been identified as a molecular feature that affects processing and presentation, thereby influencing an antigen's immunologic properties. OBJECTIVE: We assessed how changes in fold stability modulate the immunogenicity and sensitization capacity of the major birch pollen allergen Bet v 1. METHODS: By exploiting an exhaustive virtual mutation screening, we generated mutants of the prototype allergen Bet v 1 with enhanced thermal and chemical stability and rigidity. Structural changes were analyzed by means of x-ray crystallography, nuclear magnetic resonance, and molecular dynamics simulations. Stability was monitored by using differential scanning calorimetry, circular dichroism, and Fourier transform infrared spectroscopy. Endolysosomal degradation was simulated in vitro by using the microsomal fraction of JAWS II cells, followed by liquid chromatography coupled to mass spectrometry. Immunologic properties were characterized in vitro by using a human T-cell line specific for the immunodominant epitope of Bet v 1 and in vivo in an adjuvant-free BALB/c mouse model. RESULTS: Fold stabilization of Bet v 1 was pH dependent and resulted in resistance to endosomal degradation at a pH of 5 or greater, affecting presentation of the immunodominant T-cell epitope in vitro. These properties translated in vivo into a strong allergy-promoting TH2-type immune response. Efficient TH2 cell activation required both an increased stability at the pH of the early endosome and efficient degradation at lower pH in the late endosomal/lysosomal compartment. CONCLUSIONS: Our data indicate that differential pH-dependent fold stability along endosomal maturation is an essential protein-inherent determinant of allergenicity.

Aptamer-conjugated, fluorescent gold nanorods as potential cancer theradiagnostic agents.

GNRs are emerging as a new class of probes for theradiagnostic applications thanks to their unique optical properties. However, the achievement of proper nanoconstructs requires the synthesis of highly pure GNRs with well-defined aspect ratio (AR), in addition to extensive surface chemistry modification to provide them with active targeting and, possibly, multifunctionality. In this work, we refined the method of the seed mediated growth and developed a robust procedure for the fabrication of GNRs with specific AR. We also revealed and characterized unexplored aging phenomena that follow the synthesis and consistently alter GNRs' final AR. Such advances appreciably improved the feasibility of GNRs fabrication and offered useful insights on the growth mechanism. We next produced fluorescent, biocompatible, aptamer-conjugated GNRs by performing ligand exchange followed by bioconjugation to anti-cancer oligonucleotide AS1411. In vitro studies showed that our nanoconstructs selectively target cancer cells while showing negligible cytotoxicity. As a result, our aptamer-conjugated GNRs constitute ideal cancer-selective multifunctional probes and promising candidates as photothermal therapy agents.

Bioluminescence-based high-throughput screen identifies pharmacological agents that target neurotransmitter signaling in small cell lung carcinoma.

BACKGROUND: Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative. METHODS AND FINDINGS: We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC(1280) compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability. CONCLUSIONS: The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development.