Search

AbstractBackground:After officer-involved shootings (OIS), rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEOs) after lethal force incidents.Methods:Retrospective analysis of open-source video footage of OIS occurring from February 15, 2013 through December 31, 2020. Frequency and nature of care provided, time until LEO and Emergency Medical Services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board.Results:Three hundred forty-two (342) videos were included in the final analysis; LEOs rendered care in 172 (50.3%) incidents. Average elapsed time from time-of-injury (TOI) to LEO-provided care was 155.8 (SD = 198.8) seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO versus EMS care (P = .1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (P < .00001).Conclusions:It was found that LEOs rendered medical care in one-half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate profiles. The prodrug is completely independent of biotransformations and animal-independent because it becomes an active compound via a pH-triggered intramolecular cyclization–elimination reaction. As a proof-of-concept, the utility of this novel amino AOCOM ether prodrug approach was demonstrated on an antimalarial compound series representing a variety of antimalarial 4(1H)-quinolones, which entered and failed preclinical development over the last decade. With the amino AOCOM ether prodrug moiety, the 3-aryl-4(1H)-quinolone preclinical candidate was shown to provide single-dose cures in a rodent malaria model at an oral dose of 3 mg/kg, without the use of an advanced formulation technique.

Trichothecenes (TCNs) are a large group of tricyclic sesquiterpenoid mycotoxins that have intriguing structural features and remarkable biological activities. Herein, we focused on three TCNs (anguidine, verrucarin A, and verrucarol) and their ability to target both the blood and liver stages of Plasmodiumspecies, the parasite responsible for malaria. Anguidine and verrucarin A were found to be highly effective against the blood and liver stages of malaria, while verrucarol had no effect at the highest concentration tested. However, these compounds were also found to be cytotoxic and, thus, not selective, making them unsuitable for drug development. Nonetheless, they could be useful as chemical probes for protein synthesis inhibitors due to their direct impact on parasite synthesis processes.

I have also unearthed a few silver coins of George V and VI, mostly sixpences (Fig.5), although I did once find a solitary George V silver threepence. A Love of Silver My most favourite of all metals to find is silver, whether coins or artefacts. So far, my best silver find would have to be a piece made by an African artist and fashioned into the face of a leopard (Fig.4). [Extracted from the article]

Introduction:After officer-involved shootings, rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEO) after lethal force incidents.Method:Retrospective analysis of open-source video footage of officer-involved shootings (OIS) occurring between 2/15/2013 and 12/31/2020. Frequency and nature of care provided, time until LEO and emergency medical services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board.Results:342 videos were included in the final analysis. LEOs rendered care in 172 (50.3%) incidents. The average elapsed time from the time of injury to LEO-provided care was 155.8 + 198.8 seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO vs EMS care (p = 0.1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (p < 0.00001).Conclusion:LEO rendered medical care in half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

ABSTRACTIntraerythrocytic development of the human malaria parasite Plasmodium falciparumappears as a continuous flow through growth and proliferation. To develop a greater understanding of the critical regulatory events, we utilized piggyBacinsertional mutagenesis to randomly disrupt genes. Screening a collection of piggyBacmutants for slow growth, we isolated the attenuated parasite C9, which carried a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500. This gene encodes a protein structurally similar to a mitogen-activated protein kinase (MAPK) phosphatase, except for two notable characteristics that alter the signature motif of the dual-specificity phosphatase domain, suggesting that it may be a low-activity phosphatase or pseudophosphatase. C9 parasites demonstrated a significantly lower growth rate with delayed entry into the S/M phase of the cell cycle, which follows the stage of maximum PF3D7_1305500 expression in intact parasites. Genetic complementation with the full-length PF3D7_1305500 rescued the wild-type phenotype of C9, validating the importance of the putative protein phosphatase PF3D7_1305500 as a regulator of pre-S-phase cell cycle progression in P. falciparum.

Coordinated regulation of gene expression is a hallmark of the Plasmodium falciparum asexual blood-stage development cycle. We report that carbon catabolite repressor protein 4 (CCR4)-associated factor 1 (CAF1) is critical in regulating more than 1,000 genes during malaria parasites' intraerythrocytic stages, especially egress and invasion proteins. CAF1 knockout results in mistimed expression, aberrant accumulation and localization of proteins involved in parasite egress, and invasion of new host cells, leading to premature release of predominantly half-finished merozoites, drastically reducing the intraerythrocytic growth rate of the parasite. This study demonstrates that CAF1 of the CCR4-Not complex is a significant gene regulatory mechanism needed for Plasmodium development within the human host.

ABSTRACTCoordinated regulation of gene expression is a hallmark of the Plasmodium falciparumasexual blood-stage development cycle. We report that carbon catabolite repressor protein 4 (CCR4)-associated factor 1 (CAF1) is critical in regulating more than 1,000 genes during malaria parasites' intraerythrocytic stages, especially egress and invasion proteins. CAF1 knockout results in mistimed expression, aberrant accumulation and localization of proteins involved in parasite egress, and invasion of new host cells, leading to premature release of predominantly half-finished merozoites, drastically reducing the intraerythrocytic growth rate of the parasite. This study demonstrates that CAF1 of the CCR4-Not complex is a significant gene regulatory mechanism needed for Plasmodiumdevelopment within the human host.

Background:Extended care facilities (ECFs) house unique patient populations with increased risk of out of hospital cardiac arrest (OHCA) and with unique, generally medically trained first responders initiating care prior to arrival of emergency medical services (EMS). However, little is known about bystander cardiopulmonary resuscitation (CPR) and resuscitation outcomes in this population. Our aim is to assess rate of CPR delivery prior to EMS arrival in cases of OHCA among residents ECFs across the state of Arizona.Methods:Cases of OHCA between 2016-2018, cared for by participating Arizona EMS agencies, were included if OHCA occurred at an ECF, age 18+, and was of presumed cardiac etiology. Association between survival status at discharge and bystander CPR was examined first by Chi-squared test then by logistic regression, which adjusted for important risk factors and potential confounders including: age, gender, witnessed arrest, shockable initial rhythm, and return of spontaneous circulation (ROSC) in EMS care.Results:There were 1,046 cases included in this study after excluding 32 cases with DNR and 11 with unknown bystander CPR status. Median patient age was 74 (interquartile range 64, 83). The overall rate of CPR prior to EMS arrival was 78.4% (95% CI, 75.8%, 80.9%). Survival to hospital discharge and survival with favorable neurologic outcome were not different between nursing home patients who received CPR prior to EMS arrival and those who did not [6.2% vs. 4.4% (p = 0.34) and 3.1% vs. 1.8% (p = 0.29)]. There was no statistically significant difference in the adjusted analysis.Conclusions:In this study population CPR was commonly delivered prior to EMS arrival. However, delivery of CPR prior to EMS arrival was not associated with survival to hospital discharge or favorable neurologic outcome. The lack of positive association between CPR prior to arrival and survival to hospital discharge may be related to comorbid factors present in ECF patients or differences in the time between collapse and initiation of CPR. Further study is needed to identify factors that might improve survival in this unique population.

The article offers information on lawsuits and criminal charges faced by German car manufacturer Volkswagen in the U.S. Topics discussed include the firm's act of misleading consumers about the emissions performance of many of its diesel vehicles; multidistrict litigation faced by automobile manufacturers; investigation by the U.S. Environmental Protection Agency (EPA) and California Air Resources Board (CARB) against Volkswagen.