Multi-drug-resistant infections caused by Gram-negative pathogens are rapidly increasing, highlighting the need for new chemotherapies. Unlike Gram-positive bacteria, where many different chemical ...classes of antibiotics show efficacy, Gram-negatives are intrinsically insensitive to many antimicrobials including the macrolides, rifamycins, and aminocoumarins, despite intracellular targets that are susceptible to these drugs. The basis for this insensitivity is the presence of the impermeant outer membrane of Gram-negative bacteria in addition to the expression of pumps and porins that reduce intracellular concentrations of many molecules. Compounds that sensitize Gram-negative cells to “Gram-positive antibiotics”, antibiotic adjuvants, offer an orthogonal approach to addressing the crisis of multi-drug-resistant Gram-negative pathogens. We performed a forward chemical genetic screen of 30,000 small molecules designed to identify such antibiotic adjuvants of the aminocoumarin antibiotic novobiocin in Escherichia coli. Four compounds from this screen were shown to be synergistic with novobiocin including inhibitors of the bacterial cytoskeleton protein MreB, cell wall biosynthesis enzymes, and DNA synthesis. All of these molecules were associated with altered cell shape and small molecule permeability, suggesting a unifying mechanism for these antibiotic adjuvants. The potential exists to expand this approach as a means to develop novel combination therapies for the treatment of infections caused by Gram-negative pathogens.
The Vip3Aa insecticidal protein from
(Bt) is produced by specific transgenic corn and cotton varieties for efficient control of target lepidopteran pests. The main threat to this technology is the ...evolution of resistance in targeted insect pests and understanding the mechanistic basis of resistance is crucial to deploy the most appropriate strategies for resistance management. In this work, we tested whether alteration of membrane receptors in the insect midgut might explain the >2000-fold Vip3Aa resistance phenotype in a laboratory-selected colony of
(Vip-Sel). Binding of
I-labeled Vip3Aa to brush border membrane vesicles (BBMV) from 3rd instar larvae from Vip-Sel was not significantly different from binding in the reference susceptible colony. Interestingly, BBMV from Vip-Sel larvae showed dramatically reduced levels of membrane-bound alkaline phosphatase (mALP) activity, which was further confirmed by a strong downregulation of the membrane-bound alkaline phosphatase 1 (
) gene. However, the involvement of HvmALP1 as a receptor for the Vip3Aa protein was not supported by results from ligand blotting and viability assays with insect cells expressing
.
Objectives 1. Describe key findings from this systematic review which found disparities in palliative care access span multiple domains and sociodemographic groups. 2. Recognize barriers to accessing ...palliative care and groups which most commonly encounter challenges. Background and Objective Sociodemographic disparities in access to palliative care and end-of-life care exist. Underlying structural factors contributing to access challenges have received little systematic attention. Our objective was to synthesize current literature on palliative care access, identify challenges experienced by various sociodemographic groups, and highlight implications for future research and clinical practice. Study Identification A systematic search of PubMed, CINAHL, and Embase was conducted from inception through February 2020 to identify studies on access disparities in palliative care or hospice. Data Extraction and Synthesis A Health Care Access Conceptual Framework provided structure for our analysis, which described study details, sociodemographic profiles of participants, end-of-life related measures employed, and key findings. Included studies were appraised on methodological and reporting quality. Results Twenty articles were analyzed: quantitative (n=16), qualitative (n=3), and mixed methods (n=1). Our analysis identified the main challenges to accessing palliative care within the conceptual framework were availability (n=11) and affordability (n=11). Lack of knowledge about palliative care was a common barrier noted by many patients and caregivers. Providers reported systemic barriers hindering early referral to palliative care. Sociodemographic differences in accessing palliative care were primarily found within race, ethnicity, and socioeconomic status (n=13). To a lesser extent, age, gender, and geographic location also posed access challenges. Conclusions and Implications Palliative care access is an issue across domains, impacting various sociodemographic groups. This systematic review highlights barriers and opportunities for future research to reduce inequities in palliative care access. Future research and policy should emphasize availability of palliative care services, specifically for those with restricted access. Given the economic and quality of life benefits of palliative care, affordability of services should be considered by policy makers to expand benefits to all patients.
Identifying the major forces driving variation in gut microbiomes enhances our understanding of how and why symbioses between hosts and microbes evolved. Gut prokaryotic community variation is often ...closely associated with host evolutionary and ecological variables. Whether these same factors drive variation in other microbial taxa occupying the animal gut remains largely untested. Here, we present a one-to-one comparison of gut prokaryotic (16S rRNA metabarcoding) and microeukaryotic (18S rRNA metabarcoding) community patterning among 12 species of wild lemurs. Lemurs were sampled from dry forests and rainforests of southeastern Madagascar and display a range of phylogenetic and ecological niche diversity. We found that while lemur gut prokaryotic community diversity and composition vary with host taxonomy, diet, and habitat, gut microeukaryotic communities have no detectable association with any of these factors. We conclude that gut microeukaryotic community composition is largely random, while gut prokaryotic communities are conserved among host species. It is likely that a greater proportion of gut microeukaryotic communities comprise taxa with commensal, transient, and/or parasitic symbioses compared with gut prokaryotes, many of which form long-term relationships with the host and perform important biological functions. Our study highlights the importance of greater specificity in microbiome research; the gut microbiome contains many “omes” (e.g., prokaryome, eukaryome), each comprising different microbial taxa shaped by unique selective pressures.
This is a definitive, state-of-the-art resource on the vital pieces of perinatal and pediatric palliative care. Culling the most important new evidence-based research and findings from scholars and ...practitioners worldwide, it links theoretical knowledge and clinical practice to fill a gap in current information. The text is distinguished by its provision of different and even competing perspectives that address the complexities of the tragic human experience of perinatal, neonatal, and pediatric death and the nurses and other healthcare providers who provide care to those involved. Contributors disseminate new theoretical approaches and reexamine current concepts in light of new research. They discuss the theoretical underpinnings of perinatal and pediatric bereavement, examine current thought on the dimensions of loss, deliver evidence-based clinical interventions, and offer the perspective of grieving families regarding their experiences and needs. The book provides both novice and experienced scholars of perinatal and pediatric bereavement with a strong foundation of current knowledge. With clinical interventions derived from research, the book will enhance the expertise of clinicians caring for bereaved women and their families. It Includes case studies, interview excerpts, graphics and review questions to illustrate key points, and summaries demonstrating how theory is translated to clinical practice and informs research. Chapters provide objectives, references, and suggestions for additional study. The book is also a valuable study aid for students preparing for the Pediatric Loss Certification exam.
The Oxford Handbook of Human Resource Management aims to provide an authoritative account of current trends and developments in Human Resource Management (HRM). HRM is central to management teaching ...and research, and has emerged in the last decade as a significant field from its earlier roots in personnel management, industrial relations, and industrial psychology. People Management and High Performance teams have become key functions and goals for managers at all levels in organizations. The text is divided into four parts: foundations and frameworks; core processes and functions; patterns and dynamics; and finally measurement and outcomes.
•We investigated patterns of infection with E. histolytica in a community of endangered lemurs in the eastern rainforests of Madagascar.•The results from our study represent the first evidence of E. ...histolytica in wild lemurs.•Distance to human settlements explained the variation in E. histolytica infection seen in lemurs.•These findings have implications for both conservation and human and wildlife health.
Amoebiasis, caused by Entamoeba histolytica, affects 50 million people worldwide, and results in 100,000 deaths annually. It is particularly prevalent in developing nations where poverty and poor sanitation contribute to contamination of food and water. E. histolytica is also a zoonotic protozoan parasite with the potential to infect non-human primates. Lemurs, primates endemic to Madagascar, are the most threatened mammalian group in the world due to habitat loss. As forests disappear, humans and lemurs come into more frequent contact, and the potential for E. histolytica to infect lemurs intensifies. Consequently, we screened 176 fecal samples from seven lemur species at eight sites in the rain forests of southeastern Madagascar for E. histolytica to determine if human proximity influenced lemur infection. Of samples examined, 4.0% (from three lemur species) were positive for E. histolytica. Of lemurs infected with E. histolytica, three (43%) exhibited diarrheal feces. Distance to human settlements explained the variation in E. histolytica infection seen in lemurs. These results provide the first evidence of E. histolytica in wild lemurs and highlight the need for additional work to better understand the eco-epidemiology of this potential threat to these species.
A cross-sectional evaluation of patients after surgery for adolescent idiopathic scoliosis (AIS).
To determine the agreement between patients' and parents' perceptions of the patient's postoperative ...appearance and to compare those perceptions with physical and radiographic measures of deformity.
Improving cosmesis is an important aim of surgery. Patients' appearances may influence their evaluation of its outcome.
Physical and radiographic data were collected 2 years after surgery for 128 patients with AIS. Patients and parents independently rated shoulder blades, shoulders, waist, and overall appearance. Additionally, patients completed the Quality of Life Profile for Spinal Disorders (QLPSD). Agreement was evaluated with the weighted kappa statistic ranging between 0 and 1 where higher values indicate better agreement.
Fair to moderate agreement was found between patient and parent ratings of the patient's shoulder blades (kappa = 0.39; 95% confidence interval CI, 0.29-0.48), shoulders (kappa = 0.38; 95% CI, 0.26-0.50), waist (kappa = 0.45; 95% CI, 0.25-0.55), and overall appearance (kappa = 0.22; 95% CI, 0.04-0.40). Patients rated the appearance of their waist (P = 0.013) and overall appearance (P = 0.039) significantly worse than their parents. Patients' perceptions of their overall appearance had higher correlations with the body image subscale score (r = 0.45, P = 0.000) and the total quality of life score on the QLPSD (r = 0.37, P = 0.000) than did parents' perceptions of those same measures (r = 0.21, P = 0.025; and r = 0.08, P = 0.369, respectively).
Radiographic and physical measures of deformity do not correlate well with patients' and parents' perceptions of appearance. Patients and parents do not strongly agree on the cosmetic outcome of AIS surgery. Therefore, given that the adolescents themselves undergo the surgery, patients' assessments of their deformity, rather than radiographic measures or parents' assessments, should play a major role in the evaluation of surgical success.
In traditional immuno-polymerase chain reaction (immuno-PCR), a single antibody recognition event is associated with one to three DNA tags, which are subsequently amplified by PCR. Here we describe a ...nanoparticle-amplified immuno-PCR (NPA–IPCR) assay that combines antibody recognition of enzyme-linked immunosorbent assay (ELISA) with a 50-fold nanoparticle valence amplification step prior to tag amplification by PCR. The assay detects a respiratory syncytial virus (RSV) surface protein using an antibody bound to a 15-nm gold nanoparticle cofunctionalized with thiolated DNA complementary to a hybridized 76-base tag DNA with a tag DNA/antibody ratio of 50:1. The presence of virus particles triggers the formation of a “sandwich” complex composed of the gold nanoparticle construct, virus, and an antibody-functionalized magnetic particle used for extraction. After extraction, DNA tags are released by heating to 95
°C and detected via real-time PCR. The limit of detection of the assay was compared with ELISA and reversion transcription (RT) PCR using RSV-infected HEp-2 cell extracts. NPA–IPCR showed an approximately 4000-fold improvement in the limit of detection compared with ELISA and a 4-fold improvement compared with viral RNA extraction followed by traditional RT–PCR. NPA–IPCR offers a viable platform for the development of early-stage diagnostics requiring an exceptionally low limit of detection.
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