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It is estimated that 10% to 20% of road accidents are related to fatigue, with accidents caused by drowsiness up to twice as deadly as those caused by other factors. In order to reduce these numbers, strategies such as advertising campaigns, the implementation of driving recorders in vehicles used for road transport of goods and passengers, or the use of drowsiness detection systems in cars have been implemented. Within the scope of the latter area, the technologies used are diverse. They can be based on the measurement of signals such as steering wheel movement, vehicle position on the road, or driver monitoring. Driver monitoring is a technology that has been exploited little so far and can be implemented in many different approaches. This work addresses the evaluation of a multidimensional drowsiness index based on the recording of facial expressions, gaze direction, and head position and studies the feasibility of its implementation in a low-cost electronic package. Specifically, the aim is to determine the driver's state by monitoring their facial expressions, such as the frequency of blinking, yawning, eye-opening, gaze direction, and head position. For this purpose, an algorithm capable of detecting drowsiness has been developed. Two approaches are compared: Facial recognition based on Haar features and facial recognition based on Histograms of Oriented Gradients (HOG). The implementation has been carried out on a Raspberry Pi, a low-cost device that allows the creation of a prototype that can detect drowsiness and interact with peripherals such as cameras or speakers. The results show that the proposed multi-index methodology performs better in detecting drowsiness than algorithms based on one-index detection.

Here, we report the complete metagenome-assembled genome of an uncultivated freshwater Flavobacterium sp. recovered from a nonaxenic Amoebozoa sp. culture. The chromosome was obtained from a metagenomic long-read sequencing run and was assembled as a circular element at a 51× coverage, length of 3.8 Mbp and a G+C content of 37.37%.

Purpose: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region., Methods: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region., Results: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions., Conclusions: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system., (© 2020 John Wiley & Sons Ltd.)

The objective of the study was to describe clinical, sociodemographic and habits characteristics in adults with diabetes mellitus and to study their association with health-related quality of life. A sample of 311 patients from the Diabetes Program of a university social work in the province of Córdoba was selected. Data were analyzed for the proportions and physical and mental components of the SF-36® questionnaire. 57.4% reached a level of tertiary or university education. High blood pressure was the most prevalent cardiovascular risk factor (86.8%), followed by dyslipidemia (50.6%) and obesity (46.5%). 24.8% had macrovascular complications and 29% had microvascular complications. In the physical material (FC) of quality of life the women had a 4.2 times greater opportunity to report a lower value in relation to the men. Between the ages of 50 and 70, the number of people in the CF group was three times higher, and those older than 70 years were 4 times worse than the younger ones. Macro and microvascular complications and those reporting less than 2 healthy lifestyles were twice as likely to score below the overall CF average. The association between complications and poorer quality of life is one more reason to achieve a good metabolic control, to optimize the management of risk factors, avoiding or delaying the appearance of complications.

Unlabelled: Diabetes Mellitus (DM) is a chronic noncommunicable disease with a prevalence of 9.8% in Argentina. A Chronic Disease Program was developed for monitoring of patients with DM at the Ambulatory Center of DASPU, in National University of Cordoba Argentina., Objective: To describe clinical characteristics of DM patients under a chronic disease program and to identify metabolic control variables associated with the presence of complications., Material and Methods: Observational, cross-sectional, descriptive study of DM Patients who attended at ambulatory center of DASPU since 2010. Categorical variables were described as proportions and number as mean ± SD. The comparison of means was performed using student test., Results: 1017 patients were analyzed with mean age of 61 ± 14 years, with 54.6% of male, 8.5% had type 1 DM, and 90.9% had DM type 2: O.7% had gestational DM. Cardiovascular risk factor were: hypertension in 78%, dyslipidemia in 35. 25.5% of patients had micro vascular complications and 18.6% had macro vascular complications. Coronary heart disease was the most frequent complication in 14.5% of the patients. . 69% had values of glycated hemoglobin (HbA1C) ≤ 7, 4%; the average total cholesterol was 185 mg / dl and LDL cholesterol 111 mg / dl. The average HbA1C was higher in patients with micro vascular complications, HbA1c 7.47% vs. 7.18% (p = 0.009). In patients with macrovascular complications there was no significant inverse trend, HbA1c 7.21% vs 7.26% with and without complications (p = 0.65). The average total cholesterol was lower in the group with macro vascular complications 173 mg / dl and 189 mg / dl (p = 0.001). Similar result was observed in LDL-C: 101 vs 113 mg / dl (p = 0.001) in patients with and without complications, respectively., Conclusion: Clinical characteristics of the patients under the program were similar to other studies reported in the literature, but the values of HbA1c and total cholesterol have better results, achieving optimal values in a large percentage of the population, with lower levels in patients with macrovascular complications.

The TGFβ and Ras-MAPK pathways play critical roles in cell development and cell cycle regulation, as well as in tumor formation and metastasis. In the absence of cellular transformation, these pathways operate in opposition to one another, where TGFβ maintains an undifferentiated cell state and suppresses proliferation, while Ras-MAPK pathways promote proliferation, survival and differentiation. However, in colorectal and pancreatic cancers, the opposing pathways' mechanisms are simultaneously activated in order to promote cancer progression and metastasis. Here, we highlight the roles of the TGFβ and Ras-MAPK pathways in normal and malignant states, and provide an explanation for how the concomitant activation of these pathways drives tumor biology. Finally, we survey potential therapeutic targets in these pathways.

Poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is a homolog of the host complement regulatory proteins that is conserved in various poxviruses including vaccinia (VACV) and variola. The vaccinia virus complement control protein (VCP), which inhibits complement by decaying the classical pathway C3-convertase (decay-accelerating activity), and by supporting inactivation of C3b and C4b by serine protease factor I (cofactor activity), was shown to play a role in viral pathogenesis. However, the role its individual complement regulatory activities impart in pathogenesis, have not yet been elucidated. Here, we have generated monoclonal antibodies (mAbs) that block the VCP functions and utilized them to evaluate the relative contribution of complement regulatory activities of VCP in viral pathogenesis by employing a rabbit intradermal model for VACV infection. Targeting VCP by mAbs that inhibited the decay-accelerating activity as well as cofactor activity of VCP or primarily the cofactor activity of VCP, by injecting them at the site of infection, significantly reduced VACV lesion size. This reduction however was not pronounced when VCP was targeted by a mAb that inhibited only the decay-accelerating activity. Further, the reduction in lesion size by mAbs was reversed when host complement was depleted by injecting cobra venom factor. Thus, our results suggest that targeting VCP by antibodies reduces VACV pathogenicity and that principally the cofactor activity of VCP appears to contribute to the virulence., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Herpesvirus saimiri (HVS) is a lymphotropic virus that causes T-cell lymphomas in New World primates. It encodes a structural homolog of complement control proteins named complement control protein homolog (CCPH). Previously, CCPH has been shown to inhibit C3d deposition on target cells exposed to complement. Here we have studied the mechanism by which it inactivates complement. We have expressed the soluble form of CCPH in Escherichia coli, purified to homogeneity and compared its activity to vaccinia virus complement control protein (VCP) and human complement regulators factor H and soluble complement receptor 1. The expressed soluble form of CCPH bound to C3b (KD = 19.2 microm) as well as to C4b (KD = 0.8 microm) and accelerated the decay of the classical/lectin as well as alternative pathway C3-convertases. In addition, it also served as factor I cofactor and supported factor I-mediated inactivation of both C3b and C4b. Time course analysis indicated that although its rate of inactivation of C4b is comparable with VCP, it is 14-fold more potent than VCP in inactivating C3b. Site-directed mutagenesis revealed that Arg-118, which corresponds to Lys-120 of variola virus complement regulator SPICE (a residue critical for its enhanced C3b cofactor activity), contributes significantly in enhancing this activity. Thus, our data indicate that HVS encodes a potent complement inhibitor that allows HVS to evade the host complement attack.

Vaccinia virus encodes a homolog of the human complement regulators named vaccinia virus complement control protein (VCP). It is composed of four contiguous complement control protein (CCP) domains. Previously, VCP has been shown to bind to C3b and C4b and to inactivate the classical and alternative pathway C3 convertases by accelerating the decay of the classical pathway C3 convertase and (to a limited extent) the alternative pathway C3 convertase, as well as by supporting the factor I-mediated inactivation of C3b and C4b (the subunits of C3 convertases). In this study, we have mapped the CCP domains of VCP important for its cofactor activities, decay-accelerating activities, and binding to the target proteins by utilizing a series of deletion mutants. Our data indicate the following. (i) CCPs 1 to 3 are essential for cofactor activity for C3b and C4b; however, CCP 4 also contributes to the optimal activity. (ii) CCPs 1 to 2 are enough to mediate the classical pathway decay-accelerating activity but show very minimal activity, and all the four CCPs are necessary for its efficient activity. (iii) CCPs 2 to 4 mediate the alternative pathway decay-accelerating activity. (iv) CCPs 1 to 3 are required for binding to C3b and C4b, but the presence of CCP 4 enhances the affinity for both the target proteins. These results together demonstrate that the entire length of the protein is required for VCP's various functional activities and suggests why the four-domain structure of viral CCP is conserved in poxviruses.

Recently it has been shown that kaposica, an immune evasion protein of Kaposi's sarcoma-associated herpesvirus, inactivates complement by acting on C3-convertases by accelerating their decay as well as by acting as a cofactor in factor I-mediated inactivation of their subunits C3b and C4b. Here, we have mapped the functional domains of kaposica. We show that SCRs 1 and 2 (SCRs 1-2) and 1-4 are essential for the classical and alternative pathway C3-convertase decay-accelerating activity (DAA), respectively, while the SCRs 2-3 are required for factor I cofactor activity (CFA) for C3b and C4b. SCR 3 and SCRs 1 and 4, however, contribute to optimal classical pathway DAA and C3b CFA, respectively. Binding data show that SCRs 1-4 and SCRs 1-2 are the smallest structural units required for measuring detectable binding to C3b and C4b, respectively. The heparin-binding site maps to SCR 1.