Investigation of social support as a mediator of the relationship between physical and psychological health among hospitalised patients.

AIM: To investigate the self-reported levels of social support from friends and family and from nurses as mediators of the relationship between self-rated physical and psychological condition in hospitalised patients. DESIGN: Cross-sectional study of adult inpatients at a large tertiary-care hospital in the northeast United States. METHODS: Multiple mediation analysis of survey data. RESULTS: In surveys received from 324 inpatients, one fourth of the variation in patients' self-rated psychological condition was explained by self-rated physical condition. Social support from family and friends mediated a significant proportion (11.0%) of the relationship between self-rated physical and psychological condition, however social support from nurses did not. CONCLUSION: Social support from family and friends can positively influence the psychological health of inpatients, but nurses are not an adequate replacement for the social support provided by family and friends. IMPLICATIONS FOR NURSING: Although nurses cannot replace the social support provided by family and friends, the assessment of social isolation and care planning of interventions to support patients is a fundamental nursing role. Technology to connect patients with friends and family should be used to mitigate isolation for hospitalised patients unable to receive in-person visits from loved ones. IMPACT: The influence of social support from family and friends and nurses was addressed. The study found social support from family and friends, but not nurses, to influence the relationship between physical and psychological ratings. This finding has implications for the role of nurses in the hospital setting. REPORTING METHOD: Strengthening the Reporting of Observational Studies in Epidemiology guidelines were followed.

Anaplastic nephroblastoma with peritoneal metastasis in an adult female Sprague Dawley rat.

Spontaneous nephroblastomas are uncommon tumors of laboratory rats. This report describes a spontaneous nephroblastoma with peritoneal metastasis in an 11-month-old, female Sprague Dawley rat. The rat was part of a breeding program and presented 15 days post parturition with clinical signs including tachypnea, dyspnea and abdominal distension. At necropsy, the right kidney was markedly enlarged by an expansile pale-tan to white multinodular mass with extension into the retroperitoneal space, with multifocal variably sized nodules involving the mesentery, and surface of pancreas, liver, uterus, and ovarian bursa. The rat also had severe bicavitary effusion. Histologically, the renal parenchyma of the affected kidney was replaced by a moderately cellular, poorly-demarcated, non-encapsulated, multilobulated mass that appeared to compress the adjacent renal outer medulla and cortex. Three distinct neoplastic cell populations were identified in this renal tumor: epithelial cells (convoluted and dilated tubules / rare primitive glomeruloid structures), mesenchymal (neoplastic spindle cells in connective tissue), and blastemal cells (primitive neoplastic cells). The extrarenal nodular masses were predominantly composed of neoplastic mesenchymal and pleomorphic blastemal cells. Immunohistochemically, neoplastic epithelial cells in the renal mass were positive for pancytokeratin, and blastemal cells in both renal and extrarenal masses were positive for Wilms' tumor 1 protein (WT1) and vimentin. Neoplastic mesenchymal elements in both renal and extrarenal masses were positive for vimentin. The neoplasm was negative for chromogranin A and S100. The tumor was classified as an anaplastic nephroblastoma with metastasis to the mesentery and peritoneal organs.

Changes in patient and nurse outcomes associated with magnet hospital recognition.

BACKGROUND: Research has documented an association between Magnet hospitals and better outcomes for nurses and patients. However, little longitudinal evidence exists to support a causal link between Magnet recognition and outcomes. OBJECTIVE: To compare changes over time in surgical patient outcomes, nurse-reported quality, and nurse outcomes in a sample of hospitals that attained Magnet recognition between 1999 and 2007 with hospitals that remained non-Magnet. RESEARCH DESIGN: Retrospective, 2-stage panel design using 4 secondary data sources. SUBJECTS: One hundred thirty-six Pennsylvania hospitals (11 emerging Magnets and 125 non-Magnets). MEASURES: American Nurses Credentialing Center Magnet recognition; risk-adjusted rates of surgical 30-day mortality and failure-to-rescue, nurse-reported quality measures, and nurse outcomes; the Practice Environment Scale of the Nursing Work Index. METHODS: Fixed-effects difference models were used to compare changes in outcomes between emerging Magnet hospitals and hospitals that remained non-Magnet. RESULTS: Emerging Magnet hospitals demonstrated markedly greater improvements in their work environments than other hospitals. On average, the changes in 30-day surgical mortality and failure-to-rescue rates over the study period were more pronounced in emerging Magnet hospitals than in non-Magnet hospitals, by 2.4 fewer deaths per 1000 patients (P<0.01) and 6.1 fewer deaths per 1000 patients (P=0.02), respectively. Similar differences in the changes for emerging Magnet hospitals and non-Magnet hospitals were observed in nurse-reported quality of care and nurse outcomes. CONCLUSIONS: In general, Magnet recognition is associated with significant improvements over time in the quality of the work environment, and in patient and nurse outcomes that exceed those of non-Magnet hospitals.

Application of coupled affinity-sizing chromatography for the detection of proteolyzed HSA-tagged proteins.

Coupled affinity liquid chromatography and size exclusion chromatography (ALC-SEC) is a technique that has been shown to successfully report product quality of proteins during cell expression and prior to the commencement of downstream processing chromatography steps. This method was applied to monitoring the degradation and subsequent partial remediation of a HSA-tagged protein which showed proteolysis, allowing for rapid cell line development to address this product quality dilemma. This paper outlines the novel application of this method for measuring and addressing protease-induced proteolysis.

Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R-spondin.

R-spondin proteins sensitize cells to Wnt signalling and act as potent stem cell growth factors. Various membrane proteins have been proposed as potential receptors of R-spondin, including LGR4/5, membrane E3 ubiquitin ligases ZNRF3/RNF43 and several others proteins. Here, we show that R-spondin interacts with ZNRF3/RNF43 and LGR4 through distinct motifs. Both LGR4 and ZNRF3 binding motifs are required for R-spondin-induced LGR4/ZNRF3 interaction, membrane clearance of ZNRF3 and activation of Wnt signalling. Importantly, Wnt-inhibitory activity of ZNRF3, but not of a ZNRF3 mutant with reduced affinity to R-spondin, can be strongly suppressed by R-spondin, suggesting that R-spondin primarily functions by binding and inhibiting ZNRF3. Together, our results support a dual receptor model of R-spondin action, where LGR4/5 serve as the engagement receptor whereas ZNRF3/RNF43 function as the effector receptor.

ß Integrins mediate FAK Y397 autophosphorylation of resistance arteries during eutrophic inward remodeling in hypertension.

Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVß3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, this process was completed and accompanied by a significant increase in FAK phosphorylation compared with normotensive control animals. Phosphorylated (p)FAK Y397 was coimmunoprecipitated with both ß1- and ß3-integrin-specific antibodies. In contrast, only a fraction (<10-fold) was coprecipitated with the ß3 integrin subunit in control vessels. Inhibition of eutrophic remodeling by cRGDfV treatment of TGR(mRen2)27 rats resulted in the development of smooth-muscle-cell hypertrophy and a significant further enhancement of FAK Y397 phosphorylation, but this time with exclusive coassociation of pFAK Y397 with integrin ß1. We established that phosphorylation of FAK Y397 with association with ß1 and ß3 integrins occurs with pressure-induced eutrophic remodeling. Inhibiting this process leads to an adaptive hypertrophic vascular response induced by a distinct ß1-mediated FAK phosphorylation pattern.

Site-specific protein modifications through pyrroline-carboxy-lysine residues.

Pyrroline-carboxy-lysine (Pcl) is a demethylated form of pyrrolysine that is generated by the pyrrolysine biosynthetic enzymes when the growth media is supplemented with D-ornithine. Pcl is readily incorporated by the unmodified pyrrolysyl-tRNA/tRNA synthetase pair into proteins expressed in Escherichia coli and in mammalian cells. Here, we describe a broadly applicable conjugation chemistry that is specific for Pcl and orthogonal to all other reactive groups on proteins. The reaction of Pcl with 2-amino-benzaldehyde or 2-amino-acetophenone reagents proceeds to near completion at neutral pH with high efficiency. We illustrate the versatility of the chemistry by conjugating Pcl proteins with poly(ethylene glycol)s, peptides, oligosaccharides, oligonucleotides, fluorescence, and biotin labels and other small molecules. Because Pcl is genetically encoded by TAG codons, this conjugation chemistry enables enhancements of the pharmacology and functionality of proteins through site-specific conjugation.

D-Ornithine coopts pyrrolysine biosynthesis to make and insert pyrroline-carboxy-lysine.

D-ornithine has previously been suggested to enhance the expression of pyrrolysine-containing proteins. We unexpectedly discovered that uptake of D-ornithine results in the insertion of a new amino acid, pyrroline-carboxy-lysine (Pcl) instead of the anticipated pyrrolysine (Pyl). Our feeding and biochemical studies point to specific roles of the poorly understood Pyl biosynthetic enzymes PylC and PylD in converting L-lysine and D-ornithine to Pcl and confirm intermediates in the biosynthesis of Pyl.

Representation of dark skin tones in foundational nursing textbooks: An image analysis.

PURPOSE: This study aimed to analyze and quantify the representation of dark skin tones (DST) images/graphics across fifteen foundational and clinical nursing textbooks to understand the degree of portrayed diversity in current nursing texts. BACKGROUND: The United States (U.S.) population is becoming more ethnically and racially diverse. There is a scarcity of nursing literature, studies, and educational materials on the assessment and early recognition of common skin assessment in patients with dark skin tones (DST). The underrepresentation of people with DST images in didactic material suggests that omissions of these images in educational resources may introduce bias in health care provider education and practice. METHODS: Fifteen popular foundational and clinical nursing textbooks were selected and analyzed. All the photo images and drawn graphics in these textbooks were coded according to Fitzpatrick's skin phototype (FSP) scale, which categorizes skin tone as (a) "Light" or Fitzpatrick scale I or II, (b) "Medium" or Fitzpatrick scale III or IV, and (c) "Dark" or Fitzpatrick scale V or VI. The training was provided for data collectors before analysis to ascertain good inter-rater reliability (Cohen's kappa = 0.960 for light skin tone, Cohen's kappa = 0.899 for medium skin tone, and Cohen's kappa = 0.913 for dark skin tone). RESULTS: Analysis of 14,192 photo images and drawn graphics depicting skin tone was completed across 15 foundational and clinical nursing textbooks. 12.3 % of photo images and 2.4 % of drawn graphics depicted dark skin tones, compared to 60.9 % of photo images and 82.8 % of drawn graphics that displayed light skin tones in these textbooks. CONCLUSIONS: Nursing textbooks overrepresent light skin tones and underrepresent dark skin tones. While the approximate racial distribution of the U.S. population is 59.3 % non-Hispanic-White, 13.6 % Black/African American, and 26.6 % Person of Color, the images and graphics of skin tones represented 68 % light, 15 % medium, and 9.4 % dark. RELEVANCE TO CLINICAL PRACTICE: All healthcare providers are expected and required to deliver competent clinical care to an increasingly diverse population. For teaching-learning, more visual representations of DST and comparative images between what to expect in dark, medium, and light skin tones can help improve knowledge deficits and increase health equity.

Skin Assessment in Patients with Dark Skin Tone.

ABSTRACT: There is a scarcity of nursing literature, studies, and educational materials on the assessment and early recognition of both common and serious integumentary and general health issues in people with dark skin tones. Nurses must be exposed to such learning resources to be adequately prepared to care for patients with diverse skin tones and to help reduce health disparities and promote health equity. This article provides faculty, nursing students, and clinicians with basic information about the assessment of dark skin tone and calls for action in academia and professional practice to ensure nurses and nursing students can effectively perform skin assessments in all patients.

Development of a screening tool for assessment of climate change-related heat illness in the clinical setting.

ABSTRACT: Extreme heat contributes to heat-related illnesses resulting from heat intolerance, which is the inability to maintain a thermal balance to tolerate heat stress. In the United States, heat-related mortality for older persons has almost doubled in the past 20 years. Other populations at risk for heat-related illness (HRI) include children, pregnant people, those who work outside, young people participating in outdoor sports, and at-risk populations such as Black, indigenous, and populations of color. The classic heat tolerance test used for decades monitoring physiological responses to repetitive motions is impractical across large and potentially health challenged populations and does not identify environmental or social factors or specific vulnerable populations. To address this issue, we developed a heat-related illness screening tool (HIST) to identify individuals at risk for HRI morbidity and mortality based on their physical, environmental, and social vulnerabilities with an emphasis on populations of concern. The HIST has the potential to be used as routine clinical screening in the same way as other commonly used screening tools. Heat intolerance affects patient outcomes and quality of life; therefore, early screening with a simple, easy-to-administer screening tool such as the HIST can identify people at risk and refer them to services that address heat exposure and/or create safety nets to prevent heat-related illnesses.

A Crafty Approach for Learning the Topographical Anatomy of the Cranial Nerves.

Certain neuroanatomical relationships can be complex for students to visualise and understand. This article describes creation of a simple and cheap model to help students more easily learn the relationships of the cranial nerves to each other and to the different regions of the central nervous system (forebrain and brainstem).

Occupational Heat Stress: An Overview for Nurse Practitioners.

ABSTRACT: The health impacts of climate change are pervasive and complex. The role of nurse practitioners is a key in addressing these emerging health challenges. However, few health care providers are aware of the extensive signs and symptoms that accompany climate-related health sequelae. This article explores the increasing prevalence of occupational heat stress and best practices for nurse practitioners in addressing this problem. The A CLIMATE mnemonic is a clinical tool applied to occupational heat stress and aims to address a comprehensive health assessment and proactive management. Two clinical case studies will be offered as exemplars of occupational heat stress. The cases are framed within the A CLIMATE mnemonic for health assessment and physical examination for nurse practitioner practice.

A Simple and Efficient CRISPR Technique for Protein Tagging.

Genetic knock-in using homology-directed repair is an inefficient process, requiring the selection of few modified cells and hindering its application to primary cells. Here, we describe Homology independent gene Tagging (HiTag), a method to tag a protein of interest by CRISPR in up to 66% of transfected cells with one single electroporation. The technique has proven effective in various cell types and can be used to knock in a fluorescent protein for live cell imaging, to modify the cellular location of a target protein and to monitor the levels of a protein of interest by a luciferase assay in primary cells.

Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage.

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.

Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.

BACKGROUND: Structure-based drug design (SBDD) can provide valuable guidance to drug discovery programs. Robust construct design and expression, protein purification and characterization, protein crystallization, and high-resolution diffraction are all needed for rapid, iterative inhibitor design. We describe here robust methods to support SBDD on an oral anti-cytokine drug target, human MAPKAP kinase 2 (MK2). Our goal was to obtain useful diffraction data with a large number of chemically diverse lead compounds. Although MK2 structures and structural methods have been reported previously, reproducibility was low and improved methods were needed. RESULTS: Our construct design strategy had four tactics: N- and C-terminal variations; entropy-reducing surface mutations; activation loop deletions; and pseudoactivation mutations. Generic, high-throughput methods for cloning and expression were coupled with automated liquid dispensing for the rapid testing of crystallization conditions with minimal sample requirements. Initial results led to development of a novel, customized robotic crystallization screen that yielded MK2/inhibitor complex crystals under many conditions in seven crystal forms. In all, 44 MK2 constructs were generated, ~500 crystals were tested for diffraction, and ~30 structures were determined, delivering high-impact structural data to support our MK2 drug design effort. CONCLUSION: Key lessons included setting reasonable criteria for construct performance and prioritization, a willingness to design and use customized crystallization screens, and, crucially, initiation of high-throughput construct exploration very early in the drug discovery process.

TRIAMF: A New Method for Delivery of Cas9 Ribonucleoprotein Complex to Human Hematopoietic Stem Cells.

CRISPR/Cas9 mediated gene editing of patient-derived hematopoietic stem and progenitor cells (HSPCs) ex vivo followed by autologous transplantation of the edited HSPCs back to the patient can provide a potential cure for monogenic blood disorders such as ß-hemoglobinopathies. One challenge for this strategy is efficient delivery of the ribonucleoprotein (RNP) complex, consisting of purified Cas9 protein and guide RNA, into HSPCs. Because ß-hemoglobinopathies are most prevalent in developing countries, it is desirable to have a reliable, efficient, easy-to-use and cost effective delivery method. With this goal in mind, we developed TRansmembrane Internalization Assisted by Membrane Filtration (TRIAMF), a new method to quickly and effectively deliver RNPs into HSPCs by passing a RNP and cell mixture through a filter membrane. We achieved robust gene editing in HSPCs using TRIAMF and demonstrated that the multilineage colony forming capacities and the competence for engraftment in immunocompromised mice of HSPCs were preserved post TRIAMF treatment. TRIAMF is a custom designed system using inexpensive components and has the capacity to process HSPCs at clinical scale.

Application of the social ecological model in folic acid public health initiatives.

All women of childbearing age who are capable of becoming pregnant should consume 0.4 mg/400 microg of folic acid daily. Folic acid decreases the incidence of neural tube defects in newborns. Despite continued public health initiatives, many women still do not consume the recommended daily requirement. This article analyzes the use of the social ecological model in folic acid public health initiatives and emphasizes assessing the outcomes of such initiatives.