207 research outputs found

    A Case Report of Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Tuberculosis

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    A 72-year-old woman with past medical history of hypertention and type 2 diabsetes presented to the emergency department for one day history of fevers, poor oral intake, and fatigue

    A Case Report of Tragaxofusp Causing Severe Tumor Lysis Syndrome In A Patient With Blastic Plasmacytoid Dendritic Cell Neoplasm

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    The patient was an 83-year-old male without significant past medical hsitory who presented to his primary care physician with several days of generalized malais

    Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

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    During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregulated at high AP frequencies to balance SV consumption. We show that Munc13-1-an essential SV priming protein-regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotransmission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

    ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co-expression correlates with poor prognosis in non-small cell lung cancer

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    AbstractImmunoglobulin-like transcript (ILT) 4 is critical for the inhibitory function of certain immune cells. We previously demonstrated that ILT4 is over-expressed in human non-small cell lung cancer (NSCLC) cells and is involved in tumour evasion via an unknown mechanism. In this report, we demonstrate that ILT4 increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling. In primary human NSCLC tissues, a significant positive relationship is observed between ILT4 and B7-H3 expression. ILT4/B7-H3 co-expression is significantly associated with a reduction in T infiltrating lymphoid cells and lower overall survival. In summary, ILT4 increases B7-H3 expression and ILT4/B7-H3 co-expression may be involved in NSCLC progression

    Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

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    <p>Abstract</p> <p>Background</p> <p>Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission.</p> <p>Results</p> <p>Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low <it>in vitro </it>cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells.</p> <p>Conclusion</p> <p>ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.</p

    Pericardial Effusion with Tamponade Physiology in a Patient with Multiple Myeloma

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    A 78-yeaer old African American female with a past medical history of IgA Kappa Multiple Myseloma was transfered to the Cardiovascular Intensive Care Unit (CVICU) at Thomas Jefferson University Hospital (TJUH) after being diagnosed with a pericardial effusion with tamponade physiology at an outside hospital

    SGLT2 Inhibitors in Patients with Diabetes and Cardiovascular Disease

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    Problem Definition: Multiple studies (e.g. EMPA-REG, CANVAS) demonstrate that SGLT2 Inhibitors (Inh) improve cardiac outcomes in patients with Type II Diabetes (DM2) with comorbid Cardiovascular Disease (CVD) including Heart Failure and Coronary Artery Disease. SGLT2 Inhibitors are considered standard of care for patients with DM2 and CVD. Based on literature published in European Journal of Preventative Cardiology and JACC HF, our prediction is that physicians at Thomas Jefferson University Hospital Ambulatory Practices (TJUH) under-utilize SGLT2 Inh for patients with co-morbid CVD and DM2. Aims for Improvement: Within the Jefferson Healthcare System, we sought to determine: Future Interventions The percentage of patients with an indication for an SGLT2 Inhibitor who were actually being prescribed this. How often providers within the Jefferson system were prescribing these medications, and what the barriers to prescribing are. With this information, we hoped to increase the percentage of (qualifying) patients who are on these medications as part of standard of care by 20% within one year of intervention
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