Nursing interventions for adults following a mental health crisis: A systematic review guided by trauma‐informed principles

There exists a growing need for health and service providers to respond to persons in a manner that recognizes the prevalence and impact of trauma in individuals and prevent inadvertent re‐traumatization in the routine process of care. The experience of mental health crisis in of itself can have traumatic and impactful effects on individuals. Trauma‐informed approaches to care offer a framework to provide crisis intervention responses that are based on the acknowledgement of the prevalence and impact of trauma and define trauma not by the event per se, but by the impact of an experience of trauma. The integration of trauma‐informed principles in the context of crisis intervention is a current practice gap. In order to inform a portion of a best‐practice guideline for registered nurses and the interprofessional team, a systematic literature review was conducted to primarily identify nursing interventions within four weeks of a mental health crisis, with a secondary focus on identifying particular interventions that included trauma‐informed principles. The systematic review yielded 21 quantitative and qualitative studies related to nursing interventions for mental health crisis, 10 of which referred to one or more principles of trauma‐informed approaches. There was a lack of studies on nursing interventions explicitly linked to implementation of trauma‐informed principles, highlighting future research needs and focused efforts to integrate trauma‐informed principles into crisis intervention practices.     

Worldwide prevalence of microbial agents’ coinfection among COVID‐19 patients: A comprehensive updated systematic review and meta‐analysis

BackgroundTo provide information about pathogens’ coinfection prevalence with SARS‐CoV‐2 could be a real help to save patients’ lives. This study aims to evaluate the pathogens’ coinfection prevalence among COVID‐19 patients.MethodIn order to find all of the relevant articles, we used systematic search approach. Research‐based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID‐19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed.ResultsA total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID‐19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95–26.46; I ²: 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31–18.96; I ²: 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84–17.36; I ²: 98.3%). Meta‐regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity.ConclusionWe identified a high prevalence of pathogenic microorganism coinfection among COVID‐19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID‐19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents’ coinfection with SARS‐CoV‐2.     

ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling

A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM “sheddase” function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor–driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.A Disintegrin and Metalloproteinases (ADAMs), especially ADAM-10 and -17, are the principal mediators of proteolytic ectodomain shedding on the cell surface (1). ADAMs and the closely related matrix metalloproteinases (MMPs) work together as “sheddases” to cleave hundreds of diverse transmembrane substrates including growth factor ligands, receptor tyrosine kinases (RTKs), adhesion molecules, and even proteases themselves from the cell surface. Unfortunately, little is known regarding how such a broad palette of proteolytic activity integrates to modulate behaviors such as cellular motility. Furthermore, extensive cross-talk and complexity among signaling networks, proteases, and their substrates make understanding sheddase regulation on a component-by-component basis challenging (2). Therapeutics have targeted sheddases and their substrates for the treatment of invasive diseases such as cancer, yet many of these inhibitors have failed in clinical trials (3). Therefore, a need exists for understanding how the balance of sheddase-mediated degradation integrates multiple layers of signaling networks to coordinately influence cell behavior in various disease contexts.Here we study how sheddase activity contributes to cell migration in the invasive disease of endometriosis, defined by the presence of endometrial-like tissue residing outside the uterus. Up to 10% of adult females and 40% of infertile women have the disease, which also exhibits comorbidity with several cancers (4, 5). Endometriosis currently has no cure: hormonal therapies merely manage the disease with significant side effects, and surgery provides only temporary relief for many, with recurrence rates as great as 40% within 5 y postoperation (6). Like cancer, endometriosis is associated with aberrant cell invasion into ectopic organ sites, and endometriotic tissues often exhibit dysregulated molecular pathways commonly perturbed in other invasive diseases. Mitogenic and inflammatory phospho-signaling [for example, phosphorylated extracellular-signal-related kinase 1/2 (p-Erk1/2), phosphorylated protein kinase B (p-Akt), and phosphorylated p38 mitogen-activated protein kinase (p-p38)], RTKs (including epidermal growth factor receptor, EGFR), and metalloproteinases have all been clinically associated with endometriosis (7, 8), and consequently represent attractive therapeutic strategies (9–11).Many challenges in developing targeted therapeutics stem from network-level complexities such as compensatory feedback, and recent work has demonstrated how critical such mechanisms are to achieving therapeutic success, especially in cancer (12, 13). Computational models of systems-level biochemical networks have shown promise as tools to understand how multiple enzymatic reactions integrate to impact overall biological behavior, often with the goal of aiding the design of personalized or combination therapies (14, 15). Considering its complex role in disease, sheddase regulation represents an ideal application of such network-level approaches. In this work, we apply the “cue–signal–response” (CSR) paradigm (14, 15) (Fig. 1A) to examine how disease-implicated growth-factor cues interact with experimentally monitored phospho-protein and protease networks (collectively referred to as signals), ultimately to influence cellular migration response. Computational modeling elucidates quantitative and predictive relationships among multiple layers of experimental data and offers testable hypotheses of context-dependent behavior and signaling feedback. We find ADAM-10 and -17 to be critical regulators of motility that are dynamically controlled through several signaling pathways, thereby affecting cell behavior through both positive feedback from EGF ligand release and negative feedback from Hepatocyte Growth Factor Receptor (HGFR; MET), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4 RTK shedding. We find kinase inhibition generally reduces ADAM-10 and -17 activities, reduces subsequent RTK shedding, and consequently allows the accumulated RTKs to enhance downstream c-Jun N-terminal kinase (Jnk) and p38 signaling. Thus, here we demonstrate an ADAM-10 and -17–based mechanism of rapidly acquired resistance to kinase inhibition through reduced RTK shedding that can be overcome with combination therapy. Targeted proteomic analysis of clinical samples from endometriosis patients indeed confirms growth-factor–driven ADAM-10 activity and consequent MET shedding are dysregulated with disease. Overall, our results have wide implications for designing combination therapies and identifying context-dependent personalized therapeutic strategies for both kinase and protease inhibitors.Open in a separate windowFig. 1.CSR study design. (A) CSR overview: we stimulate endometriotic cells with a panel of growth factor cues; record multiple downstream signals comprising measurements of phospho-signaling, sheddase regulation, and sheddase substrate regulation; and use computational modeling to map these observations onto cell migration responses. (B) Overview of signals and responses included in the CSR dataset. All receptors shown were directly measured and/or stimulated. (C) Experimental timeline of CSR study. Dark colored lines denote measurement time points. At lower left, cell migration is depicted as single-cell tracks, where initial cell positions were centered for visualization.     

Effectiveness of home versus hospital phototherapy for term infants with uncomplicated hyperbilirubinemia: a pilot study in Pahang, Malaysia

A comparative pilot study was conducted to determine the difference in the reduction of total serum bilirubin in a group of infants who had phototherapy at home compared to an in-patient group on hospital phototherapy. Eighteen infants with unconjugated hyperbilirubinaemia who fitted the selection criteria were put under the mobile home unit (Bluelite Portable Light) placed in the home. A control group of 18 infants with the same matching characteristics had intense phototherapy in the hospital using a unit with top and bottom light sources. The infants were matched for race, starting total serum bilirubin level, birth weight (up to 250 grams) and age of baby at initiation of phototherapy (up to one-day difference). It was observed that the mean daily decrease in serum bilirubin concentration was significantly more in the home group as compared to the hospital group (t=2.95, df=17, P<0.05). The mean duration of treatment was significantly less for the home group as compared to the hospital group (t=2.84, df=17, P<0.05). None of the infants who had home phototherapy were re-hospitalized. Phototherapy related complications were mild and comparable in both groups. The result suggests that home phototherapy is safe and effective in bringing down the concentration of serum bilirubin for term babies with uncomplicated hyperbilirubinaemia.     

Spontaneous tumor lysis syndrome and secondary thrombotic thrombocytopenic purpura in early stage colorectal cancer

Acute tumor lysis syndrome (ATLS) is a well-described oncological emergency that is usually associated with hematological malignan-cies complicated by treatment. It is typically related to a high tumor burden, rapidly growing and chemosensitive malignancies.