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  • 1
    Language: English
    In: Experimental Parasitology, January 2019, Vol.196, pp.28-37
    Description: is a genus of single celled parasites capable of infecting a wide range of animals including humans. species are members of the phylum apicomplexa, which includes well-known genera such as and . parasites cause a severe gastro-intestinal disease known as cryptosporidiosis. They are one of the most common causes of childhood diarrhoea worldwide, and infection can have prolonged detrimental effects on the development of children, but also can be life threatening to HIV/AIDS patients and transplant recipients. A variety of hosts can act as reservoirs, and can persist in the environment for prolonged times as oocysts. While there has been substantial interest in these parasites, there is very little progress in terms of treatment development and understanding the majority of the life cycle of this unusual organism. In this review, we will provide an overview on the existing knowledge of the biology of the parasite and the current progress in developing cultivation systems. We will then describe a synopsis of current and next generation approaches that could spearhead further research in combating the parasite.
    Keywords: Biology ; Zoology
    ISSN: 0014-4894
    E-ISSN: 1090-2449
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  • 2
    Language: English
    In: Chest, August 2015, Vol.148(2), pp.365-374
    Description: There are few data regarding mechanical ventilation and ARDS in the ED. This could be a vital arena for prevention and treatment. This study was a multicenter, observational, prospective, cohort study aimed at analyzing ventilation practices in the ED. The primary outcome was the incidence of ARDS after admission. Multivariable logistic regression was used to determine the predictors of ARDS. We analyzed 219 patients receiving mechanical ventilation to assess ED ventilation practices. Median tidal volume was 7.6 mL/kg predicted body weight (PBW) (interquartile range, 6.9-8.9), with a range of 4.3 to 12.2 mL/kg PBW. Lung-protective ventilation was used in 122 patients (55.7%). The incidence of ARDS after admission from the ED was 14.7%, with a mean onset of 2.3 days. Progression to ARDS was associated with higher illness severity and intubation in the prehospital environment or transferring facility. Of the 15 patients with ARDS in the ED (6.8%), lung-protective ventilation was used in seven (46.7%). Patients who progressed to ARDS experienced greater duration in organ failure and ICU length of stay and higher mortality. Lung-protective ventilation is infrequent in patients receiving mechanical ventilation in the ED, regardless of ARDS status. Progression to ARDS is common after admission, occurs early, and worsens outcome. Patient- and treatment-related factors present in the ED are associated with ARDS. Given the limited treatment options for ARDS, and the early onset after admission from the ED, measures to prevent onset and to mitigate severity should be instituted in the ED. ; No.: NCT01628523; URL:
    Keywords: Medicine
    ISSN: 0012-3692
    E-ISSN: 1931-3543
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  • 3
    In: Miller, Christopher N. and Jossé, Lyne and Tsaousis, Anastasios D. (2018) Localization of a Fe-S biosynthesis in Cryptosporidium mitosome. Journal of Eukaryotic Microbiology, .
    Description: Cryptosporidium is a protozoan, apicomplexan, parasite that poses significant risk to humans and animals, as a common cause of potentially fatal diarrhea in immunodeficient hosts. The parasites have evolved a number of unique biological features that allow them to thrive in a highly specialized parasitic lifestyle. For example, the genome of Cryptosporidium parvum is highly reduced, encoding only 3,805 proteins, which is also reflected in its reduced cellular and organellar content and functions. As such, its remnant mitochondrion, dubbed a mitosome, is one of the smallest mitochondria yet found. While numerous studies have attempted to discover the function(s) of the C. parvum mitosome, most of them have been focused on in silico predictions. Here, we have localized components of a biochemical pathway in the C. parvum mitosome, in our investigations into the functions of this peculiar mitochondrial organelle. We have shown that three proteins involved in the mitochondrial iron-sulfur cluster biosynthetic pathway are localized in the organelle, and one of them can functionally replace its yeast homolog. Thus, it seems that the C. parvum mitosome is involved in iron-sulfur cluster biosynthesis, supporting the organellar and cytosolic apoproteins. These results spearhead further research on elucidating the functions of the mitosome and broaden our understanding in the minimalistic adaptations of these organelles.
    Keywords: QR Microbiology
    ISSN: 1066-5234
    Source: University of Kent
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  • 4
    Language: English
    In: The Journal of eukaryotic microbiology, November 2018, Vol.65(6), pp.913-922
    Description: Cryptosporidium is a protozoan, apicomplexan, parasite that poses significant risk to humans and animals, as a common cause of potentially fatal diarrhea in immunodeficient hosts. The parasites have evolved a number of unique biological features that allow them to thrive in a highly specialized parasitic lifestyle. For example, the genome of Cryptosporidium parvum is highly reduced, encoding only 3,805 proteins, which is also reflected in its reduced cellular and organellar content and functions. As such, its remnant mitochondrion, dubbed a mitosome, is one of the smallest mitochondria yet found. While numerous studies have attempted to discover the function(s) of the C. parvum mitosome, most of them have been focused on in silico predictions. Here, we have localized components of a biochemical pathway in the C. parvum mitosome, in our investigations into the functions of this peculiar mitochondrial organelle. We have shown that three proteins involved in the mitochondrial iron-sulfur cluster biosynthetic pathway are localized in the organelle, and one of them can functionally replace its yeast homolog. Thus, it seems that the C. parvum mitosome is involved in iron-sulfur cluster biosynthesis, supporting the organellar and cytosolic apoproteins. These results spearhead further research on elucidating the functions of the mitosome and broaden our understanding in the minimalistic adaptations of these organelles.
    Keywords: Apicomplexans ; Immunofluorescence Assay ; Iron-Sulfur Clusters ; Mitochondria ; Mitosomes
    ISSN: 10665234
    E-ISSN: 1550-7408
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  • 5
    Language: English
    In: JAMA, 03 February 2015, Vol.313(5), pp.471-82
    Description: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P 〈 .001) and platelets (12 U vs 6 U, P 〈 .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. clinicaltrials.gov Identifier: NCT01545232.
    Keywords: Blood Component Transfusion -- Methods ; Exsanguination -- Therapy ; Shock, Hemorrhagic -- Therapy ; Wounds and Injuries -- Therapy
    ISSN: 00987484
    E-ISSN: 1538-3598
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  • 6
    Language: English
    In: American Journal of Emergency Medicine, December 2018, Vol.36(12), pp.2219-2224
    Description: We aim to evaluate the effectiveness of a broadly inclusive, comparatively low intensity intervention linking ED patients to a primary care home. This retrospective cohort study evaluated ED patients referred for primary care linkage in a large, urban, academic ED. A care coordination specialist performed a brief interview to gauge access barriers and provide a clinic referral with optional scheduling assistance. Data were abstracted from program records and the electronic medical record. The primary outcome was the proportion of referred individuals who attended at least one primary care appointment. Secondary outcomes included return ED encounters within one year, and factors associated with linkage outcomes. There were 2142 referrals made for 2064 patients; 1688/2142 accepted assistance. Linkage was successful for 1059/1688 (63%, CI95 60% to 65%). Among patients accepting assistance, those without successful linkage were younger (41 vs 45 years, difference 3 years, CI95 2 to 3), more often male (62% vs 55%,difference 7%, CI95 2% to 12%), and less likely to have a chronic medical condition (37% vs 45%, difference 8%; CI95 3% to 12%) or to have had an appointment scheduled within two weeks (26% vs 33%, difference 7%, CI95 2% to 12%). Insurance status and self-reported barriers to care were not associated with linkage success. Patterns of subsequent ED use were similar, regardless of referral status or linkage outcome. Low intensity, broadly inclusive, ED care coordination linked nearly 50% of patients referred for intervention, and two-thirds of willing participants, with a primary care home.
    Keywords: Care-Coordination ; Emergency Department ; Medicine
    ISSN: 0735-6757
    E-ISSN: 1532-8171
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  • 7
    In: American Journal of Hematology, February 2018, Vol.93(2), pp.159-168
    Description: Limited evidence guides opioid dosing strategies for acute Sickle Cell (SCD) pain. We compared two National Heart, Lung and Blood (NHBLI) recommended opioid dosing strategies (weight‐based vs. patient‐specific) for ED treatment of acute vaso‐occlusive episodes (VOE). A prospective randomized controlled trial (RCT) was conducted in two ED's. Adults ≥ 21 years of age with SCD disease were eligible. Among the 155 eligible patients, 106 consented and 52 had eligible visits. Patients were pre‐enrolled in the outpatient setting and randomized to one of two opioid dosing strategies for a future ED visit. ED providers accessed protocols through the electronic medical record. Change in pain score (0‐100 mm VAS) from arrival to ED disposition, as well as side effects were assessed. 52 patients (median age was 27 years, 42% were female, and 89% black) had one or more ED visits for a VOE (total of 126 ED study visits, up to 5 visits/patient were included). Participants randomized to the patient‐specific protocol experienced a mean reduction in pain score that was 16.6 points greater than patients randomized to the weight‐based group (mean difference 95% CI = 11.3 to 21.9,  = 0.03). Naloxone was not required for either protocol and nausea and/or vomiting was observed less often in the patient‐specific protocol (25.8% vs 59.4%,  = 0.0001). The hospital admission rate for VOE was lower for patients in the patient‐specific protocol (40.3% vs 57.8%  = 0.05). NHLBI guideline‐based analgesia with patient‐specific opioid dosing resulted in greater improvements in the pain experience compared to a weight‐based strategy, without increased side effects.
    Keywords: Emergency ; Pain ; Sickle Cell Disease ; Vaso‐Occlusive Crisis
    ISSN: 0361-8609
    E-ISSN: 1096-8652
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  • 8
    Language: English
    In: Journal of cell science, 09 April 2018, Vol.131(7)
    Description: Although the Golgi complex has a conserved morphology of flattened stacked cisternae in most eukaryotes, it has lost the stacked organisation in several lineages, raising the question of what range of morphologies is possible for the Golgi. In order to understand this diversity, it is necessary to characterise the Golgi in many different lineages. Here, we identify the Golgi complex in , one of the first descriptions of an unstacked Golgi organelle in a non-parasitic eukaryote, other than fungi. We provide a comprehensive list of Golgi-associated membrane trafficking genes encoded in two species of and show that nearly all are expressed in mouse-passaged cells. We then study distribution of the Golgi marker ()CopB by fluorescence in , identifying membranous structures that are disrupted by Brefeldin A treatment, consistent with Golgi localisation. Confocal and immunoelectron microscopy reveals that COPB localises to tubular membranous structures. Our data identify the Golgi organelle for the first time in this major eukaryotic lineage, and provide the rare example of a tubular morphology, representing an important sampling point for the comparative understanding of Golgi organellar diversity.This article has an associated First Person interview with the first author of the paper.
    Keywords: Brefeldin A ; Copi ; Dictyosome ; Evolutionary Cell Biology ; Membrane Trafficking ; Protist ; Phylogeny ; Golgi Apparatus -- Genetics ; Membrane Transport Proteins -- Genetics ; Naegleria -- Cytology
    ISSN: 00219533
    E-ISSN: 1477-9137
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  • 9
    Language: English
    In: International Journal for Parasitology, March 2018, Vol.48(3-4), pp.197-201
    Description: parasites are a major cause of diarrhoea that pose a particular threat to children in developing areas and immunocompromised individuals. Curative therapies and vaccines are lacking, mainly due to lack of a long-term culturing system of this parasite. Here, we show that COLO-680N cells infected with two different strains produce sufficient infectious oocysts to infect subsequent cultures, showing a substantial fold increase in production, depending on the experiment, over the most optimistic HCT-8 models. Oocyst identity was confirmed using a variety of microscopic- and molecular-based methods. This culturing system will accelerate research on and the development of anti- drugs.
    Keywords: Cryptosporidium ; Cell Culture ; Colo-680n ; Lipidomics ; Proteomics ; Atomic Force Microscopy ; Immunofluorescence Microscopy ; Electron Microscopy ; Biology ; Zoology
    ISSN: 0020-7519
    E-ISSN: 1879-0135
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  • 10
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States, May 7, 2013, Vol.110(19), p.7586(6)
    Description: Tissue vascularization and integration with host circulation remains a key barrier to the translation of engineered tissues into clinically relevant therapies. Here, we used a microtissue molding approach to demonstrate that constructs containing highly aligned "cords" of endothelial cells triggered the formation of new capillaries along the length of the patterned cords. These vessels became perfused with host blood as early as 3 d post implantation and became progressively more mature through 28 d. Immunohistochemical analysis showed that the neovessels were composed of human and mouse endothelial cells and exhibited a mature phenotype, as indicated by the presence of alpha-smooth muscle actin-positive pericytes. Implantation of cords with a prescribed geometry demonstrated that they provided a template that defined the neovascular architecture in vivo. To explore the utility of this geometric control, we implanted primary rat and human hepatocyte constructs containing randomly organized endothelial networks vs. ordered cords. We found substantially enhanced hepatic survival and function in the constructs containing ordered i cords following transplantation in mice. These findings demonstrate the importance of multicellular architecture in tissue integration and function, and our approach provides a unique strategy to engineer vascular architecture. tissue engineering | regenerative medicine | angiogenesis | vascular biology | liver doi/10.1073/pnas.1217796110
    Keywords: Tissue Engineering -- Research ; Endothelium -- Physiological Aspects ; Immunohistochemistry -- Research
    ISSN: 0027-8424
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