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Experimental Ion Exchange Column With SuperLig 639 And Simulant Formulation

SuperLig®639 ion exchange resin was tested as a retrieval mechanism for pertechnetate, through decontamination of a perrhenate spiked 5M Simple Average Na{sup +} Mass Based Simulant. Testing included batch contacts and a three-column ion exchange campaign. A decontamination of perrhenate exceeding 99% from the liquid feed was demonstrated. Analysis of the first formulation of a SBS/WESP simulant found unexpectedly low concentrations of soluble aluminum. Follow-on work will complete the formulation

Patient Knowledge And Perception Regarding Antibiotic Misuse In Primary Care

The Centers for Disease Control (CDC) and Prevention’s 2019 Antibiotic Resistant Threats Report shows that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths in the United States each year. This equates to at least one infection every 11 seconds and one death resulting from antibiotic resistance every 15 minutes. The CDC states that there were almost twice as many deaths each year from antibiotic resistance compared to statistics reported in 2013 (CDC, 2019a). Proper antibiotic use is the responsibility of the provider and the patient. Patient knowledge should consist of how to prevent antibiotic misuse, certain disease processes that require antibiotics, and the significance of taking antibiotics as prescribed. Therefore, determining if the patient has a thorough knowledge of these particular factors could help prevent one of the major threats faced worldwide today, which is antibiotic resistance. The purpose of this study was to determine if the patient has knowledge of risk factors associated with antibiotic misuse. The researchers conducted a quantitative, descriptive study using a convenience sampling of 500 patients from eight clinics located in Mississippi. This study consisted of a voluntary questionnaire given to patients within these clinics. Prior to conducting the study, consent was obtained from the Institutional Review Board (IRB) at the Mississippi University for Women. For data collection, the researchers used a data collection questionnaire, which included demographics such as age, gender, insurance provider, and education level. After data collection, the data was subjected to analyses using descriptive statistics including knowledge, misuse, and perception regarding antibiotics. The results of this study showed this sample of respondents were quite knowledgeable about antibiotic use and thus are expected to be more likely to use antibiotics appropriately. However, those at greater risk for misuse (those less knowledgeable) are less likely to perceive that their health care provider is knowledgeable regarding antibiotic use

Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite's Chloroquine Resistance Transporter

Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transportthese drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite’s survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite’s hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite’s sensitivity to this antimalarial. These insights provide a foundation for understanding clinically-relevant observations of inverse drug susceptibilities in the malaria parasite

Rural-Urban Differences in Caregiver Burden Due to the COVID-19 Pandemic among a National Sample of Informal Caregivers

The objective of this exploratory study was to explore potential associations between changes to caregiver burden (CB) due to the COVID-19 pandemic and rural-urban status using a nationally representative sample of 761 informal caregivers. Tertiles of two measures of rural-urban status were used: Rural-Urban Commuting Areas (RUCAs) and population density. Bivariate and multivariable binary and ordinal logistic regression were used to asses study objectives. Using RUCAs, rural informal caregivers were more than twice as likely as urban informal caregivers to report a substantial increase in CB due to COVID-19 (OR 2.27, 95% CI [1.28–4.02]). Similar results were observed for population density tertiles (OR 2.20, 95% CI [1.22–3.96]). Having a COVID-19 diagnosis was also significantly associated with increased CB. Understanding and addressing the root causes of rural-urban disparities in CB among informal caregivers is critical to improving caregiver health and maintaining this critical component of the healthcare system

Verapamil-Sensitive Transport of Quinacrine and Methylene Blue via the Plasmodium falciparum Chloroquine Resistance Transporter Reduces the Parasite's Susceptibility to these Tricyclic Drugs.

BACKGROUND: It is becoming increasingly apparent that certain mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) alter the parasite's susceptibility to diverse compounds. Here we investigated the interaction of PfCRT with 3 tricyclic compounds that have been used to treat malaria (quinacrine [QC] and methylene blue [MB]) or to study P. falciparum (acridine orange [AO]). METHODS: We measured the antiplasmodial activities of QC, MB, and AO against chloroquine-resistant and chloroquine-sensitive P. falciparum and determined whether QC and AO affect the accumulation and activity of chloroquine in these parasites. We also assessed the ability of mutant (PfCRT(Dd2)) and wild-type (PfCRT(D10)) variants of the protein to transport QC, MB, and AO when expressed at the surface of Xenopus laevis oocytes. RESULTS: Chloroquine resistance-conferring isoforms of PfCRT reduced the susceptibility of the parasite to QC, MB, and AO. In chloroquine-resistant (but not chloroquine-sensitive) parasites, AO and QC increased the parasite's accumulation of, and susceptibility to, chloroquine. All 3 compounds were shown to bind to PfCRT(Dd2), and the transport of QC and MB via this protein was saturable and inhibited by the chloroquine resistance-reverser verapamil. CONCLUSIONS: Our findings reveal that the PfCRT(Dd2)-mediated transport of tricyclic antimalarials reduces the parasite's susceptibility to these drugs

Multiple drugs compete for transport via the Plasmodium falciparum chloroquine resistance transporter at distinct but interdependent sites

Mutations in the "chloroquine resistance transporter" (PfCRT) are a major determinant of drug resistance in the malaria parasite Plasmodium falciparum. We have previously shown that mutant PfCRT transports the antimalarial drug chloroquine away from its target, whereas the wild-type form of PfCRT does not. However, little is understood about the transport of other drugs via PfCRT or the mechanism by which PfCRT recognizes different substrates. Here we show that mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses revealed that chloroquine and quinine compete for transport via PfCRT in a manner that is consistent with mixed-type inhibition. Moreover, our analyses suggest that PfCRT accepts chloroquine and quinine at distinct but antagonistically interacting sites. We also found verapamil to be a partial mixed-type inhibitor of chloroquine transport via PfCRT, further supporting the idea that PfCRT possesses multiple substratebinding sites. Our findings provide new mechanistic insights into the workings of PfCRT, which could be exploited to design potent inhibitors of this key mediator of drug resistance

Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite's chloroquine resistance transporter

Mutations in the chloroquine resistance transporter (PfCRT) are the primary determinant of chloroquine (CQ) resistance in the malaria parasite Plasmodium falciparum. A number of distinct PfCRT haplotypes, containing between 4 and 10 mutations, have give

Exploring Gender Bias in Nursing Evaluations of Emergency Medicine Residents

Objectives Nursing evaluations are an important component of residents’ professional development as nurses are present for interactions with patients and nonphysician providers. Despite this, there has been few prior studies on the benefits, harms, or effectiveness of using nursing evaluations to help guide emergency medicine residents’ development. We hypothesized that gender bias exists in nursing evaluations and that female residents, compared to their male counterparts, would receive more negative feedback on the perception of their interpersonal communication skills. Methods Data were drawn from nursing evaluations of residents between March 2013 and April 2016. All comments were coded if they contained words falling into four main categories: standout, ability, grindstone, and interpersonal. This methodology and the list of words that guided coding were based on the work of prior scholars. Names and gendered pronouns were obscured and each comment was manually reviewed and coded for valence (positive, neutral, negative) and strength (certain or tentative) by at least two members of the research team. Following the qualitative coding, quantitative analysis was performed to test for differences. To evaluate whether any measurable differences in ability between male and female residents existed, we compiled and compared American Board of Emergency Medicine in‐training examination scores and relevant milestone evaluations between female and male residents from the same period in which the residents were evaluated by nursing staff. Results Of 1,112 nursing evaluations, 30% contained comments. Chi‐square tests on the distribution of valence (positive, neutral, or negative) indicated statistically significant differences in ability and grindstone categories based on the gender of the resident. A total of 51% of ability comments about female residents were negative compared to 20% of those about male residents (χ2 = 11.83, p < 0.01). A total of 57% of grindstone comments about female residents were negative as opposed 24% of those about male residents (χ2 = 6.03, p < 0.01). Conclusions Our findings demonstrate that, despite the lack of difference in ability or competence as measured by in‐service examination scores and milestone evaluations, nurses evaluate female residents lower in their abilities and work ethic compared to male residents