An evaluation of an educational intervention to reduce inappropriate cannulation and improve cannulation technique by paramedics

Background: Intravenous cannulation enables administration of fluids or drugs by paramedics in prehospital settings. Inappropriate use and poor technique carry risks for patients, including pain and infection. We aimed to investigate the effect of an educational intervention designed to reduce the rate of inappropriate cannulation and to improve cannulation technique. Method: We used a non-randomised control group design, comparing two counties in the East Midlands (UK)as intervention and control areas. The educational intervention was based on Joint Royal Colleges Ambulance Liaison Committee guidance and delivered to paramedic team leaders who cascaded it to their teams. We analysed rates of inappropriate cannulation before and after the intervention using routine clinical data. We also assessed overall cannulation rates before and after the intervention. A sample of paramedics was assessed post-intervention on cannulation technique with a ‘‘model’’ arm using a predesigned checklist. Results: There was a non-significant reduction in inappropriate (no intravenous fluids or drugs given) cannulation rates in the intervention area (1.0% to 0%) compared with the control area (2.5% to 2.6%). There was a significant (p,0.001) reduction in cannulation rates in the intervention area (9.1% to 6.5%; OR 0.7, 95% CI 0.48 to 1.03) compared with an increase in the control area (13.8% to 19.1%; OR 1.47, 95% CI 1.15 to 1.90), a significant difference (p,0.001). Paramedics in the intervention area were significantly more likely to use correct hand-washing techniques post-intervention (74.5% vs. 14.9%; p,0.001). Conclusion: The educational intervention was effective in bringing about changes leading to enhanced quality and safety in some aspects of prehospital cannulation

A rare presentation of disseminated invasive aspergillosis

Here’s presenting a case of disseminated invasive aspergillosis in a young female patient with pulmonary and CNS complications and the difficulty one faces while diagnosing such a case due to variable presentation of symptoms with no prior history of any underlying immunodeficiency. It also focuses on how diagnosing such a case can be further delayed due to clinical and radiological miss-match. Thus, it is important to have a high index of suspicion in such patients as prolonged antibiotics and systemic steroids worsens the course of illness.

Aalap: AI Assistant for Legal & Paralegal Functions in India

Using proprietary Large Language Models on legal tasks poses challenges due to data privacy issues, domain data heterogeneity, domain knowledge sophistication, and domain objectives uniqueness. We created Aalalp, a fine-tuned Mistral 7B model on instructions data related to specific Indian legal tasks. The performance of Aalap is better than gpt-3.5-turbo in 31\% of our test data and obtains an equivalent score in 34\% of the test data as evaluated by GPT4. Training Aalap mainly focuses on teaching legal reasoning rather than legal recall. Aalap is definitely helpful for the day-to-day activities of lawyers, judges, or anyone working in legal systems

Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

<p>Abstract</p> <p>Background</p> <p>New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process.</p> <p>Results</p> <p>We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under <it>in vitro </it>conditions and recruited to bind with blood vessels on gel-foam under <it>in vivo </it>conditions. The degree of recruitment of pericytes into <it>in vitro </it>neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells.</p> <p>Conclusion</p> <p>These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.</p

Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood.</p> <p>Results</p> <p>We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1.</p> <p>Conclusions</p> <p>In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.</p

Alterations in Platelet Secretion Differentially Affect Thrombosis and Hemostasis

We genetically manipulated the major platelet vesicle-associated membrane proteins (VAMP2, VAMP3, and VAMP8) to create mice with varying degrees of disrupted platelet secretion. As previously shown, loss of VAMP8 reduced granule secretion, and this defect was exacerbated by further deletion of VAMP2 and VAMP3. VAMP2Δ3Δ8−/− platelets also had reduced VAMP7. Loss of VAMP2 and VAMP3 (VAMP2Δ3Δ) had a minimal impact on secretion when VAMP7 and VAMP8 were present. Integrin αIIbβ3 activation and aggregation were not affected, although spreading was reduced in VAMP2Δ3Δ8−/− platelets. Using these mice as tools, we asked how much secretion is needed for proper thrombosis and hemostasis in vivo. VAMP2Δ3Δ mice showed no deficiency, whereas VAMP8−/− mice had attenuated formation of occlusive thrombi upon FeCl3-induced arterial injury but no excessive bleeding upon tail transection. VAMP2Δ3Δ8−/− mice bled profusely and failed to form occlusive thrombi. Plasma-coagulation factors were normal in all of the strains, but phosphatidylserine exposure was reduced in VAMP2Δ3Δ and VAMP2Δ3Δ8−/− platelets. From our data, an ∼40% to 50% reduction in platelet secretion in vitro (dense and α granule) correlated with reduced occlusive thrombosis but no compromise in hemostasis. At a \u3e 50% reduction, thrombosis and hemostasis were defective in vivo. Our studies are the first systematic manipulation of platelet exocytic machinery to demonstrate a quantitative linkage between in vitro platelet secretion and hemostasis and thrombosis in vivo. The animals described will be invaluable tools for future investigations into how platelet secretion affects other vascular processes

A Theory-Grounded Measure of Adolescents\u27 Response to Media Literacy Interventions

Media literacy interventions offer relatively new and promising avenues for the prevention of risky health behaviors among children and adolescents, but current literature remains largely equivocal about their efficacy. We propose that (a) much of this ambiguity stems from the lack of conceptual clarity in the literature regarding the cognitive process through which media literacy interventions influence their target audience, and (b) that the ability to track this cognitive process by means of valid and reliable measures is necessary to evaluating the effects of media literacy programs on their audience. Accordingly, the primary objective of this study was to develop and test theoretically-grounded measures of audiences’ degree of engagement with the content of media literacy programs based on the recognition that engagement (and not participation per se) can better explain and predict individual variations in the effects of these programs. We tested the validity and reliability of this measure with two different samples of 10th grade high school students (Study I N = 294; Study II N = 171) who participated in a pilot and actual test of a brief media literacy curriculum. Responses to an inventory of items measuring evaluation of the media literacy program underwent an exploratory factor analysis for Study I. Four message evaluation factors (involvement, perceived novelty, critical thinking, personal reflection) emerged and were confirmed through CFA (Study II), demonstrating acceptable reliability as scales as well as item-level convergent validity and convergent and discriminant validity with other measures. We discuss the implications of including process of effect measures in the design and evaluation of media literacy interventions

Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis

A role for apoptosis-inducing factor in T cell development

Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the β-selection stage, independent of T cell receptor β recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding–deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity–deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic β-selection