Experiences of cohabiting partners of women diagnosed with cancer during pregnancy: a qualitative study.

PURPOSE: When a pregnant woman is diagnosed with cancer, she faces complex and unique challenges while navigating both obstetric and oncological care. Despite often being the primary support for women diagnosed with cancer during pregnancy (CDP), little is known about the experiences of their partners. We undertook an in-depth exploration of the experiences of partners of women diagnosed with CDP in Australia. METHODS: Semi-structured interviews were conducted with partners of women diagnosed with CDP treated in Australia. Interviews explored partners' inclusion in decision making and communication with health professionals and their own coping experiences. Data were analysed thematically. RESULTS: Data from interviews with 12 male partners (N = 12) of women diagnosed with CDP were analysed. Two unique themes relevant to partners were identified: 'Partners require support to adjust to changing roles and additional burdens' and 'Treating the couple as a team facilitates agency and coping, but partners' needs are placed second by all'. CONCLUSION: Partners of women diagnosed with CDP commonly experience unique stressors and a substantial shift in previously established roles across multiple domains including medical advocacy, household coordination and parenting. Partners' coping is interlinked with how the woman diagnosed with CDP is coping. Inclusion of partners in treatment decisions and communications, and considering partners' wellbeing alongside that of the woman with CDP, is likely to be supportive for partners. In turn, this is likely to enhance the quality of support that women diagnosed with CDP receive from their partners.

Development and preliminary validation of a novel eating disorder screening tool for vegetarians and vegans: the V-EDS.

BACKGROUND: Eating disorders have one of the highest mortality of all mental illnesses but are associated with low rates of screening and early intervention. In addition, there remains considerable uncertainty regarding the use of current standardised screening tools in measuring eating pathology in vegetarians and vegans. With these groups presenting as potential at-risk groups for disordered eating development, the present study aimed to develop and preliminary validate a novel eating disorder screening tool, the Vegetarian Vegan Eating Disorder Screener (V-EDS). METHODS: We utilised a mixed-methods approach, comprising four phases. RESULTS: A conceptual framework was developed from 25 community, clinician, and lived experience interviews and used to derive a preliminary set of 163 items (Phase 1). Phase 2 piloted the items to establish face and content validity through cognitive debriefing interviews of 18 additional community, clinician, and lived experience participants, resulting in a reduced, revised questionnaire of 53 items. Phase 3 involved scale purification using Item Response Theory in analysis of 230 vegetarians and 230 vegans resulting in a further reduced 18-item questionnaire. Phase 4 validated the screening tool in a large community sample of 245 vegetarians and 405 vegans using traditional psychometric analysis, finding the V-EDS supports a unidimensional factor structure with excellent internal consistency (α = 0.95-0.96) and convergent validity (0.87-0.88), and moderate discriminate validity (0.45-0.55). CONCLUSIONS: This study provided strong initial support for the psychometric validity and theoretical assumptions of the novel V-EDS screening tool. The V-EDS has the potential to increase early intervention rates for vegetarians and vegans experiencing eating disorder symptoms, further supporting advocacy and treatment approaches for these expanding dietary groups.

The present study describes the development and preliminary validation of the first screening tool designed to uniquely assess eating disorder symptoms in individuals following a vegetarian or vegan diet. Following several development phases, the final version of the Vegetarian Vegan Eating Disorder Screener (V-EDS) comprises 18-items, with six dietary characteristic items and 12 eating disorder scored items. The current findings support excellent initial reliability and validity of the V-EDS. The V-EDS constitutes a promising tool that could potentially be integrated as a standalone measure for initial screening in clinical and research settings, but also for more comprehensive assessment when combined with other gold-standard eating disorder tools.

Changes to the activity and sensitivity of nerves innervating subchondral bone contribute to pain in late-stage osteoarthritis.

ABSTRACT: Although it is clear that osteoarthritis (OA) pain involves activation and/or sensitization of nociceptors that innervate knee joint articular tissues, much less is known about the role of the innervation of surrounding bone. In this study, we used monoiodoacetate (MIA)-induced OA in male rats to test the idea that pain in OA is driven by differential contributions from nerves that innervate knee joint articular tissues vs the surrounding bone. The time-course of pain behavior was assayed using the advanced dynamic weight-bearing device, and histopathology was examined using haematoxylin and eosin histology. Extracellular electrophysiological recordings of knee joint and bone afferent neurons were made early (day 3) and late (day 28) in the pathogenesis of MIA-induced OA. We observed significant changes in the function of knee joint afferent neurons, but not bone afferent neurons, at day 3 when there was histological evidence of inflammation in the joint capsule, but no damage to the articular cartilage or subchondral bone. Changes in the function of bone afferent neurons were only observed at day 28, when there was histological evidence of damage to the articular cartilage and subchondral bone. Our findings suggest that pain early in MIA-induced OA involves activation and sensitization of nerves that innervate the joint capsule but not the underlying subchondral bone, and that pain in late MIA-induced OA involves the additional recruitment of nerves that innervate the subchondral bone. Thus, nerves that innervate bone should be considered important targets for development of mechanism-based therapies to treat pain in late OA.

Initiative to Reduce Antibiotic Exposure of Asymptomatic Infants Born to Mothers with Intraamniotic Infection.

Infants born to mothers with intraamniotic infection (IAI) received antibiotic treatment per the Centers for Disease Control and Prevention and American Academy of Pediatrics guidelines in our neonatal intensive care unit (NICU) for early-onset bacterial sepsis evaluation. We conducted a quality improvement project to decrease antibiotic use and NICU admission in infants born to mothers with IAI. METHODS: We aimed to decrease the antibiotic exposure for asymptomatic infants born to mothers with IAI from 100% to 20% in 6 months. We obtained baseline data on these infants from January 2018 to January 2019, with the intervention starting in February 2019. A new standardized guideline to clinically monitor and follow laboratories on asymptomatic infants in couplet care was created with a multidisciplinary team's help and implemented after provider education. The team reviewed data monthly and used PDSA cycles to make necessary changes, including updating order sets, more educational handouts, and real-time coaching to both nurses and physicians. RESULTS: There was a dramatic decline (93%-0%) in antibiotic exposure and NICU admission after implementing this guideline. There was also a decrease in IAI diagnosis. There were no readmissions of infants for infection within 30 days of discharge, and there were no positive blood cultures. CONCLUSIONS: Implementing best antibiotic stewardship practices through a standardized guideline, testing, implementation of processes, and education by a multidisciplinary team limited the antibiotic exposure and NICU admissions for infants born to mothers with IAI with no known increase in readmissions.

Intensive management of obesity in people with severe chronic kidney disease: A review.

Obesity is highly prevalent worldwide, including among people with chronic kidney disease (CKD). The presence of severe and/or end-stage kidney disease complicates the treatment of obesity for several reasons, including restrictions on protein and fluid intake and renal excretion of several medications indicated for the treatment of obesity. The aim of this review is to assess the safety of intensive obesity treatments, such as very-low-energy diets (VLEDs), obesity pharmacotherapy and/or bariatric surgery, in people with end-stage kidney disease. A literature search was conducted to identify studies reporting safety outcomes for VLEDs, liraglutide, phentermine, phentermine-topiramate, naltrexone-bupropion and bariatric surgery in people with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2 or on dialysis. Limited data were insufficient to recommend VLEDs but highlighted their potential efficacy and the need for close clinical and biochemical monitoring. There were no data regarding centrally acting obesity pharmacotherapy in this population, although some glucagon-like peptide-1 analogues appear to safely induce weight loss at doses used for the treatment of type 2 diabetes. Some studies suggest an increased rate of complications of bariatric surgery in individuals with severe or end-stage CKD. Further prospective evaluation of intensive obesity management in the growing population with obesity and severe, end-stage and dialysis-dependent CKD is required.

An 'eFP-Seq Browser' for visualizing and exploring RNA sequencing data.

Improvements in next-generation sequencing technologies have resulted in dramatically reduced sequencing costs. This has led to an explosion of '-seq'-based methods, of which RNA sequencing (RNA-seq) for generating transcriptomic data is the most popular. By analysing global patterns of gene expression in organs/tissues/cells of interest or in response to chemical or environmental perturbations, researchers can better understand an organism's biology. Tools designed to work with large RNA-seq data sets enable analyses and visualizations to help generate hypotheses about a gene's function. We present here a user-friendly RNA-seq data exploration tool, called the 'eFP-Seq Browser', that shows the read map coverage of a gene of interest in each of the samples along with 'electronic fluorescent pictographic' (eFP) images that serve as visual representations of expression levels. The tool also summarizes the details of each RNA-seq experiment, providing links to archival databases and publications. It automatically computes the reads per kilobase per million reads mapped expression-level summaries and point biserial correlation scores to sort the samples based on a gene's expression level or by how dissimilar the read map profile is from a gene splice variant, to quickly identify samples with the strongest expression level or where alternative splicing might be occurring. Links to the Integrated Genome Browser desktop visualization tool allow researchers to visualize and explore the details of RNA-seq alignments summarized in eFP-Seq Browser as coverage graphs. We present four cases of use of the eFP-Seq Browser for ABI3, SR34, SR45a and U2AF65B, where we examine expression levels and identify alternative splicing. The URL for the browser is https://bar.utoronto.ca/eFP-Seq_Browser/. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. Tool is at https://bar.utoronto.ca/eFP-Seq_Browser/; RNA-seq data at https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/ and https://s3.amazonaws.com/iplant-cdn/iplant/home/araport/rnaseq_bam/Klepikova/. Code is available at https://github.com/BioAnalyticResource/eFP-Seq-Browser.

Proteome-wide, Structure-Based Prediction of Protein-Protein Interactions/New Molecular Interactions Viewer.

Determining the complete Arabidopsis (Arabidopsis thaliana) protein-protein interaction network is essential for understanding the functional organization of the proteome. Numerous small-scale studies and a couple of large-scale ones have elucidated a fraction of the estimated 300,000 binary protein-protein interactions in Arabidopsis. In this study, we provide evidence that a docking algorithm has the ability to identify real interactions using both experimentally determined and predicted protein structures. We ranked 0.91 million interactions generated by all possible pairwise combinations of 1,346 predicted structure models from an Arabidopsis predicted "structure-ome" and found a significant enrichment of real interactions for the top-ranking predicted interactions, as shown by cosubcellular enrichment analysis and yeast two-hybrid validation. Our success rate for computationally predicted, structure-based interactions was 63% of the success rate for published interactions naively tested using the yeast two-hybrid system and 2.7 times better than for randomly picked pairs of proteins. This study provides another perspective in interactome exploration and biological network reconstruction using protein structural information. We have made these interactions freely accessible through an improved Arabidopsis Interactions Viewer and have created community tools for accessing these and ∼2.8 million other protein-protein and protein-DNA interactions for hypothesis generation by researchers worldwide. The Arabidopsis Interactions Viewer is freely available at http://bar.utoronto.ca/interactions2/.

Current development of biodegradable polymeric materials for biomedical applications.

In the last half-century, the development of biodegradable polymeric materials for biomedical applications has advanced significantly. Biodegradable polymeric materials are favored in the development of therapeutic devices, including temporary implants and three-dimensional scaffolds for tissue engineering. Further advancements have occurred in the utilization of biodegradable polymeric materials for pharmacological applications such as delivery vehicles for controlled/sustained drug release. These applications require particular physicochemical, biological, and degradation properties of the materials to deliver effective therapy. As a result, a wide range of natural or synthetic polymers able to undergo hydrolytic or enzymatic degradation is being studied for biomedical applications. This review outlines the current development of biodegradable natural and synthetic polymeric materials for various biomedical applications, including tissue engineering, temporary implants, wound healing, and drug delivery.

Fibromodulin reduces scar size and increases scar tensile strength in normal and excessive-mechanical-loading porcine cutaneous wounds.

Hypertrophic scarring is a major postoperative complication which leads to severe disfigurement and dysfunction in patients and usually requires multiple surgical revisions due to its high recurrence rates. Excessive-mechanical-loading across wounds is an important initiator of hypertrophic scarring formation. In this study, we demonstrate that intradermal administration of a single extracellular matrix (ECM) molecule-fibromodulin (FMOD) protein-can significantly reduce scar size, increase tensile strength, and improve dermal collagen architecture organization in the normal and even excessive-mechanical-loading red Duroc pig wound models. Since pig skin is recognized by the Food and Drug Administration as the closest animal equivalent to human skin, and because red Duroc pigs show scarring that closely resembles human proliferative scarring and hypertrophic scarring, FMOD-based technologies hold high translational potential and applicability to human patients suffering from scarring-especially hypertrophic scarring.

Nfatc1 Is a Functional Transcriptional Factor Mediating Nell-1-Induced Runx3 Upregulation in Chondrocytes.

Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3-promoter in response to Nell-1 treatment. By revealing the Nell-1 → Nfatc1 → Runx3 → Ihh cascade, we demonstrate the involvement of Nfatc1, a nuclear factor of activated T-cells, in chondrogenesis, while providing innovative insights into developing a novel therapeutic strategy for cartilage regeneration and other chondrogenesis-related conditions.

Disease Association and Druggability of WD40 Repeat Proteins.

WD40 repeat (WDR) domains are protein interaction scaffolds that represent one of the largest protein families in human, and a first WDR inhibitor-an allosteric antagonist of polycomb repressive complex 2-just entered the clinic. A systematic analysis of the CORUM database of protein complexes shows that WDR is the most represented domain in transcriptional regulation and one of the most prevalent in the ubiquitin proteasome system, two pathways of high relevance to drug discovery. Parsing the literature and the vulnerability of cancer cell lines to CRISPR knockout indicates that WDR proteins are targets of interest in oncology and other disease areas. A quantitative analysis of WDR structures reveals that druggable binding pockets can be found on multiple surfaces of these multifaceted protein interaction platforms. These data support the development of chemical probes to further interrogate WDR proteins as an emerging therapeutic target class.

Do Patients With a Baseline Clinical Condition Warranting the Cautious Use of Parenteral Nutrition Develop Subsequent Metabolic Complications?

BACKGROUND: The American Society for Parenteral and Enteral Nutrition Adult Nutrition Support Core Curriculum describes clinical conditions that warrant cautious use of parenteral nutrition (CCWCPN). The Core Curriculum authors acknowledge there is no evidence for specific criteria suggested for the clinical conditions. Consequently, the purpose of this study was to determine the impact of a baseline CCWCPN on the development of subsequent metabolic complications in patients receiving parenteral nutrition (PN). METHODS: Adult patients initiated on PN from May 2014 to July 2015 at Cooper University Hospital were included in this retrospective study. The impact of a CCWCPN on the development of the following was determined: acid-base disturbances, hepatobiliary complications, hypercapnia, hyperchloremia, hyperglycemia, hypernatremia, hypertriglyceridemia, hypochloremia, hypoglycemia, hypokalemia, hypophosphatemia, and refeeding syndrome. RESULTS: Three hundred forty-one patients were included (mean age, 61.7 years; mean duration of PN, 8.5 days; central PN, 97%). Metabolic complications occurred more frequently in patients with a baseline CCWCPN than without these conditions (77% vs 53%, P = .001). Subgroup analyses for the development of metabolic complications in patients with or without each individual baseline CCWCPN yielded the following statistically significant results: hypernatremia (93% vs 57%, P = .007) and hyperchloremia (86% vs 57%, P = .033). CONCLUSIONS: Hospitalized adult patients with a baseline CCWCPN were more likely to develop a metabolic complication when receiving PN. Baseline hypernatremia and hyperchloremia were associated with the development of metabolic complications. Baseline CCWCPN should be recognized upon initiation of PN; practitioners should closely monitor patients to minimize subsequent metabolic complications.

Generation, Expansion, and Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) Derived From the Umbilical Cords of Newborns.

The umbilical cord is tissue that is normally discarded after the delivery of the infant, but it has been shown to be a rich source of stem cells from the cord blood, Wharton's jelly, and umbilical endothelial cells. Patient-specific human induced pluripotent stem cells (hiPSCs) reprogrammed from patient specific human umbilical vein endothelial cells in the neonatal intensive care unit (NICU) population (specifically, premature neonates) have not been shown in the literature. This unit describes a protocol for the generation and expansion of hiPSCs originating from umbilical cords collected from patients in the NICU.

Cell death in Escherichia coli dnaE(Ts) mutants incubated at a nonpermissive temperature is prevented by mutation in the cydA gene.

Cells of the Escherichia coli dnaE(Ts) dnaE74 and dnaE486 mutants die after 4 h of incubation at 40 degrees C in Luria-Bertani medium. Cell death is preceded by elongation, is inhibited by chloramphenicol, tetracycline, or rifampin, and is dependent on cell density. Cells survive at 40 degrees C when they are incubated at a high population density or at a low density in conditioned medium, but they die when the medium is supplemented with glucose and amino acids. Deletion of recA or sulA has no effect. We isolated suppressors which survived for long periods at 40 degrees C but did not form colonies. The suppressors protected against hydroxyurea-induced killing. Sequence and complementation analysis indicated that suppression was due to mutation in the cydA gene. The DNA content of dnaE mutants increased about eightfold in 4 h at 40 degrees C, as did the DNA content of the suppressed strains. The amount of plasmid pBR322 in a dnaE74 strain increased about fourfold, as measured on gels, and the electrophoretic pattern appeared to be normal even though the viability of the parent cells decreased 2 logs. Transformation activity also increased. 4',6'-diamidino-2-phenylindole staining demonstrated that there were nucleoids distributed throughout the dnaE filaments formed at 40 degrees C, indicating that there was segregation of the newly formed DNA. We concluded that the DNA synthesized was physiologically competent, particularly since the number of viable cells of the suppressed strain increased during the first few hours of incubation. These observations support the view that E. coli senses the rate of DNA synthesis and inhibits septation when the rate of DNA synthesis falls below a critical level relative to the level of RNA and protein synthesis.