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Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the genus Babesia. Treatment of this emerging malaria-related disease has relied on antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative agent of malaria, has recently been validated as a target for anti-malarial drug development and therefore, in this study, we investigated the effect of epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib and ixazomib) proteasome inhibitors on the growth and survival of Babesia. Testing the compounds against Babesia divergens ex vivo revealed suppressive effects on parasite growth with activity that was higher than the cytotoxic effects on a non-transformed mouse macrophage cell line. Furthermore, we showed that the most-effective compound, carfilzomib, significantly reduces parasite multiplication in a Babesia microti infected mouse model without noticeable adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and in vivo decrease in proteasome activity and accumulation of polyubiquitinated proteins compared to untreated control. Overall, our results demonstrate that the Babesia proteasome is a valid target for drug development and warrants the design of potent and selective B. divergens proteasome inhibitors for the treatment of babesiosis.

The disciplines of logistics and supply chain management have the potential of having many areas of emphasis. Universities that have some kind of emphasis in this field have developed programs that depend on the need of potential employers and their own faculty mix. Several studies have previously looked at how universities deal with this field at the graduate level, mainly as part of their MBA program. In this study, the authors focus on the ten universities in the United States that have the leading undergraduate programs in supply chain management. They look at each of their curriculum in terms of courses and course content and see how each of these universities satisfies a previously established knowledge set for this field of study. They realize that there will most likely never be in the foreseeable future a well-structured and agreed upon common curriculum for teaching this particular subject matter. The intended audiences are businesses that are hiring new graduates and the universities that are looking to start a similar program.

As one approach to examining the way ethical decisions are made, we asked experts (i.e., ethicists, regulatory officials, and experienced researchers) and novices (i.e., inexperienced graduate students) to review a set of scenarios that depict some important ethical tensions in research. The method employed was "protocol analysis," a talk-aloud technique pioneered by cognitive scientists for the analysis of expert performance. The participants were asked to verbalize their normally unexpressed thought processes as they responded to the scenarios, and to make recommendations for courses of action. We found that experts spent more time working through the decision-making process than novices and also raised substantially more concerns than novices. Differences also exist among the three groups of experts.

The literature suggests that administering drug surveys to public school students is best done by persons outside of the school system (or at least unfamiliar to the students). This is the approach used by the long-time "Monitoring the Future" project. Because of the increased costs that administration by outside research associates requires (both time and transportation), we decided to design an experiment that would compare it to administration by school personnel. Six school systems were split, and 3756 surveys were administered, about half by outside research associates and half by school personnel. The results indicate that there were minimal and non-significant differences between the two groups. On the basis of these results, we draw the conclusion that school personnel are able to administer survey instruments without affecting the quality of the results and, thus, that school districts may safely use such data in the evaluation of their drug education and drug prevention programs. (Contains 5 tables.)

Objectives. People with refractory epilepsy are overwhelmed by the uncertainty of their next seizures. Accurate prediction of future seizures could greatly improve the quality of life for these patients. New evidence suggests that seizure occurrences can have cyclical patterns for some patients. Even though these cyclicalities are not intuitive, they can be identified by machine learning (ML), to identify patients with predictable vs unpredictable seizure patterns. Approach. Self-reported seizure logs of 153 patients from the Human Epilepsy Project with more than three reported seizures (totaling 8337 seizures) were used to obtain inter-seizure interval time-series for training and evaluation of the forecasting models. Two classes of prediction methods were studied: (1) statistical approaches using Bayesian fusion of population-wise and individual-wise seizure patterns; and (2) ML-based algorithms including least squares, least absolute shrinkage and selection operator, support vector machine (SVM) regression, and long short-term memory regression. Leave-one-person-out cross-validation was used for training and evaluation, by training on seizure diaries of all except one subject and testing on the left-out subject. Main results. The leading forecasting models were the SVM regression and a statistical model that combined the median of population-wise seizure time-intervals with a test subject's prior seizure intervals. SVM was able to forecast 50%, 70%, 81%, 84%, and 87% of seizures of unseen subjects within 0, 1, 2, 3 to 4 d of mean absolute forecasting error, respectively. The subject-wise performances show that patients with more frequent seizures were generally better predicted. Significance. ML models can leverage non-random patterns within self-reported seizure diaries to forecast future seizures. While diary-based seizure forecasting alone is only one of many aspects of clinical care of patients with epilepsy, studying the level of predictability across seizures and patients paves the path towards a better understanding of predictable vs unpredictable seizures on individualized and population-wise bases. [ABSTRACT FROM AUTHOR]

Argues that process evaluation is needed to validate prison-based substance abuse treatment effectiveness. Five groups--inmates, treatment staff, prison staff, prison administration, and the parole board--should be a part of this process evaluation. Discusses these five groups relative to three stages of development of substance abuse treatment in prison. (RJM)

Studied how positive the educational and social experiences were for vastly outnumbered and socially segregated minority students at a predominantly white university. Responses from 240 black and white students show that minority students are daily reminded, overtly and covertly, of their minority status. The alienation from campus life this causes forces minorities into their own social cliques. (GR)

Suggests the bachelor's paper as an alternative to testing for sociology majors. Explains that the paper enables the student to use the discipline's theoretical and methodological tools to address an important topic. Explores the advantages and disadvantages of the paper. Suggests that the assignment promotes assessment both of the student and the program. (SG)

Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity. [ABSTRACT FROM AUTHOR]

The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms. [ABSTRACT FROM AUTHOR]

Case managers have been viewed as engaging in direct practice, community practice, or both. This article offers a third view: Case managers also engage in the practice of management. Employing Mintzberg's seminal research on chief executive behavior, the authors argue that case managers' work is similarly characterized by brevity, variety, and fragmentation. Case managers perform the 10 roles developed in Mintzberg's original study. These roles are divided into three groups: interpersonal, including figurehead, leader, and liaison; informational, including monitor, disseminator, and spokesperson; and decision-making, including entrepreneur, disturbance handler, resource allocator, and negotiator. Case managers' tasks associated with each role are presented. Considering their work as managerial in nature will help case managers more effectively assist clients in goal achievement., The prominence of case management as a service delivery method and as an area of study for social workers has increased in the past decade. Although case management has its [...]