Compelling evidence from preclinical and clinical studies has shown that mild to moderate hypothermia is neuroprotective against ischemic stroke. Clinical applications of hypothermia therapy, however, have been hindered by current methods of physical cooling, which is generally inefficient and impractical in clinical situations. In this report, we demonstrate the potential of pharmacologically induced hypothermia (PIH) by the novel neurotensin receptor 1 (NTR1) agonist ABS-201 in a focal ischemic model of adult mice. ABS-201 (1.5-2.5 mg/kg, i.p.) reduces body and brain temperature by 2-5°C in 15-30 min in a dose-dependent manner without causing shivering or altering physiological parameters. Infarct volumes at 24 h after stroke are reduced by ∼30-40% when PIH therapy is initiated either immediately after stroke induction or after 30-60 min delay. ABS-201 treatment increases bcl-2 expression, decreases caspase-3 activation, and TUNEL-positive cells in the peri-infarct region, and suppresses autophagic cell death compared to stroke controls. The PIH therapy using ABS-201 improves recovery of sensorimotor function as tested 21 d after stroke. These results suggest that PIH induced by neurotensin analogs represented by ABS-201 are promising candidates for treatment of ischemic stroke and possibly for other ischemic or traumatic injuries.
Background Little remains known about both Asian and Asian American (A/AA) and non-Asian young adults’ experiences and affective reactions regarding COVID-19 anti-Asian discrimination. To our knowledge, this is the first study that explores the nature and impact of COVID-19 anti-Asian discrimination within a multi-racial sample. Methods This study uses qualitative open-ended responses from a sub-sample of Wave I of the COVID-19 Adult Resilience Experiences Study (CARES) data collected between March to September 2020. Thematic analysis was used to explore two open-ended questions: “Are there experiences we missed in the survey so far that you wish to describe?” and “What are your thoughts about the current social climate?” The data analysis for this study focused on 113 discrimination or racism-related comments. Results A total of 1331 young adults completed an online survey of which 611 provided comments; a multi-racial sample of 95 individuals (65.3% non-Asians, 24.7% A/AA) contributed 113 COVID-19 anti-Asian discrimination or racism-related comments. Two overarching themes were: types of discrimination (societal, interpersonal, intrapersonal) and affective reactions to discrimination (fear, anxiety/distress, hopelessness/depression, and avoidance). Not only did both A/AA and non-Asian participants report witnessing or hearing reports of anti-Asian discrimination, but both groups described having negative affective reactions to anti-Asian discrimination. Conclusion Anti-Asian discrimination in the face of COVID may be more widespread than initial reports indicate. Our finding suggests that anti-Asian discrimination is a societal illness that impacts all populations in the U.S. This calls for cross-racial coalitions and solidarity in the fight against discrimination and racism.
We compared the in vitro effect of boric acid (BA) versus phenylboronic acid (PBA) on the migration of prostate and breast cancer cell lines and non-tumorigenic cells from the same tissues. Treatment at 24 hours with BA (≤500 μM) did not inhibit chemotaxis on fibronectin in any cell line. However, treatment over the same time course with concentrations of PBA as low as 1 μM significantly inhibited cancer cell migration without effecting nontumorigenic cell lines. The compounds did not affect cell adhesion or viability at 24 hours but did alter morphology; both decreased cancer cell viability at eight days. These results suggest that PBA is more potent than BA in targeting the metastatic and proliferative properties of cancer cells.
Hemorrhagic stroke, including intracerebral hemorrhage (ICH), is a devastating subtype of stroke; yet, effective clinical treatment is very limited. Accumulating evidence has shown that mild to moderate hypothermia is a promising intervention for ischemic stroke and ICH. Current physical cooling methods, however, are less efficient and often impractical for acute ICH patients. The present investigation tested pharmacologically induced hypothermia (PIH) using the second generation neurotensin receptor (NTR) agonist HPI-201 (formerly known as ABS-201) in an adult mouse model with ICH. Acute or delayed administrations of HPI-201 (2 mg/kg bolus injection followed by 2 injections of 1 mg/kg, i.p.) were initiated at 1 or 24 hrs after ICH. HPI-201 induced mild hypothermia within 30 min and maintained body and brain temperatures at 32.7±0.4°C for at least 6 hrs without causing observable shivering. With the 1 hr delayed treatment, HPI-201-induced PIH significantly reduced ICH-induced cell death and brain edema compared to saline-treated ICH animals. When HPI-201-induced hypothermia was initiated 24 hrs after the onset of ICH, it still significantly attenuated brain edema, cell death and blood brain barrier breakdown. HPI-201 significantly decreased the expression of MMP-9, reduced caspase-3 activation, and increased Bcl-2 expression in the ICH brain. Moreover, ICH mice received 1-hr delayed HPI-201 treatment performed significantly better in the neurological behavior test 48 hrs after ICH. All together, these data suggest that systemic injection of HPI-201 is an effective hypothermic strategy that protects the brain from ICH injury with a wide therapeutic window. The protective effect of this PIH therapy is partially mediated through the alleviation of apoptosis and neurovascular damage. We suggest that pharmacological hypothermia using the newly developed neurotensin analogs is a promising therapeutic treatment for ICH.
Urinary tract infections (UTIs) are among the most common healthcare-associated infections, and 70%-80% are catheter-associated urinary tract infections (CAUTIs). About 25% of hospitalized patients have an indwelling urinary catheter placed during their hospital stay, and therefore, are at risk for CAUTIs which have been associated with worse patient outcomes. Additionally, hospitals face a significant financial impact since the Centers for Medicare and Medicaid Services incentive program penalizes hospitals with higher than expected CAUTIs. Hospitalists care for many patients with indwelling urinary catheters and should be aware of and engage in processes that reduce the rate of CAUTIs. This article will discuss the diagnosis, treatment, and prevention of CAUTIs in adults.
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