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Active Matrix Metalloprotease-9 Is Associated with the Collagen Capsule Surrounding the Madurella mycetomatis Grain in Mycetoma
Kirsten Geneugelijk,Wendy Kloezen,Ahmed H. Fahal,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002754
Abstract: Madurella mycetomatis is the main causative organism of eumycetoma, a persistent, progressive granulomatous infection. After subcutaneous inoculation M. mycetomatis organizes itself in grains inside a granuloma with excessive collagen accumulation surrounding it. This could be contributing to treatment failure towards currently used antifungal agents. Due to their pivotal role in tissue remodelling, matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) or tissue inhibitor of metalloproteinases (TIMP) might be involved in this process. Local MMP-2 and MMP-9 expression was assessed by immunohistochemistry while absolute serum levels of these enzymes were determined in mycetoma patients and healthy controls by performing ELISAs. The presence of active MMP was determined by gelatin zymography. We found that both MMP-2 and MMP-9 are expressed in the mycetoma lesion, but the absolute MMP-2, -9, and TIMP-1 serum levels did not significantly differ between patients and controls. However, active MMP-9 was found in sera of 36% of M. mycetomatis infected subjects, whereas this active form was absent in sera of controls (P<0.0001). MMP-2, MMP-9, and TIMP-1 polymorphisms in mycetoma patients and healthy controls were determined through PCR-RFLP or sequencing. A higher T allele frequency in TIMP-1 (+372) SNP was observed in male M. mycetomatis mycetoma patients compared to controls. The presence of active MMP-9 in mycetoma patients suggest that MMP-9 is activated or synthesized by inflammatory cells upon M. mycetomatis infection. Inhibiting MMP-9 activity with doxycycline could prevent collagen accumulation in mycetoma, which in its turn might make the fungus more accessible to antifungal agents.
A Madurella mycetomatis Grain Model in Galleria mellonella Larvae
Wendy Kloezen,Marilyn van Helvert-van Poppel?,Ahmed H. Fahal?,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2015, DOI: 10.1371/journal.pntd.0003926
Abstract: Eumycetoma is a chronic granulomatous subcutaneous infectious disease, endemic in tropical and subtropical regions and most commonly caused by the fungus Madurella mycetomatis. Interestingly, although grain formation is key in mycetoma, its formation process and its susceptibility towards antifungal agents are not well understood. This is because grain formation cannot be induced in vitro; a mammalian host is necessary to induce its formation. Until now, invertebrate hosts were never used to study grain formation in M. mycetomatis. In this study we determined if larvae of the greater wax moth Galleria mellonella could be used to induce grain formation when infected with M. mycetomatis. Three different M. mycetomatis strains were selected and three different inocula for each strain were used to infect G. mellonella larvae, ranging from 0.04 mg/larvae to 4 mg/larvae. Larvae were monitored for 10 days. It appeared that most larvae survived the lowest inoculum, but at the highest inoculum all larvae died within the 10 day observation period. At all inocula tested, grains were formed within 4 hours after infection. The grains produced in the larvae resembled those formed in human and in mammalian hosts. In conclusion, the M. mycetomatis grain model in G. mellonella larvae described here could serve as a useful model to study the grain formation and therapeutic responses towards antifungal agents in the future.
Madurella mycetomatis Is Highly Susceptible to Ravuconazole
Sarah Abdalla Ahmed ,Wendy Kloezen,Frederick Duncanson,Ed E. Zijlstra,G. Sybren de Hoog,Ahmed H. Fahal,Wendy W. J. van de Sande
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002942
Abstract: The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤0.002 and 0.031 μg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.
The Head Stands Accused by the Heart! —Depression and Premature Death from Ischaemic Heart Disease  [PDF]
Wendy Thomson
Open Journal of Depression (OJD) , 2014, DOI: 10.4236/ojd.2014.32008
Abstract: Background: The purpose of this study was to examine whether clinical depression was associated with higher risk of premature death from ischemic heart disease (IHD). Risk for IHD was examined separately by sex and sub-type of depression in a long-term follow-up study spanning 49 years. Method: Patients who were diagnosed with depression in the Chichester/Salisbury Catchment Area Study were followed for 49 years. Observed deaths from IHD prior to the age of 70 were compared with rates that were predicted from historical data on mortality rates from 1960 onwards. Results: Significantly higher rates of death from IHD before the age of 70 were found among males with endogenous depression. Conclusions: The results are discussed in terms of the broader literature on mortality from natural causes among patients with clinical depression. In terms of prevention, the results indicate that patients diagnosed with severe clinical depression particularly men at the very least warrant risk assessment with regard to IHD.
Infection Prevention Strategies in Cardiac Rehabilitation [1]—A Behavioral Intervention for Patients [2]  [PDF]
Wendy Bjerke
Health (Health) , 2017, DOI: 10.4236/health.2017.99092
Abstract: Background: Healthcare Acquired Infections (HAI) result in over 100 thousand deaths each year with one third of these deaths preventable via behaviors such as hand washing among health care providers in inpatient settings. Less research has been conducted in outpatient exercise settings such as cardiac rehabilitation (CR) among patients. Purpose: The purpose of this study was to examine the effectiveness of HAI prevention strategies in a CR setting among patients. Methods: Observations of the frequency of hand washing among CR patients pre and post four HAI strategies including provision of HAI education and signs, hand washing demonstrations, a HAI prevention video, and hand sanitizer samples. Washing hands prior to CR (WI) was observed as well as washing hands prior to leaving the CR center (WO). Methods included recording the frequency of WI and WO among all patients at baseline and after each of the four interventions. Mean frequencies of WI and WO were compared among a mean of 22 - 43 CR patient visits over 12 weeks using descriptive statistics and t-tests to determine if changes were significant pre and post intervention strategies. Results: At baseline, no patients WI or WO during an outpatient CR visit. Post interventions 1 - 4, the percentage of patients WI and WO was 33 and 34, 32 and 26, 32 and 29, 33 and 22 respectively. At a one-year follow up, the percentage of patients WI and WO was 40%. Conclusion: Increases in frequency and the percentage of WI and WO were observed among patients meriting continued examination of HAI prevention strategies among patients in outpatient exercise settings such as CR.
Genetic and health issues emerging from sperm donation—The experiences and views of donors  [PDF]
Ken Daniels, Wendy Kramer
Advances in Reproductive Sciences (ARSci) , 2013, DOI: 10.4236/arsci.2013.13003
Abstract: 164 previous sperm donors completed an online survey regarding health and genetic experiences and views. Results highlight that donors desire to act responsibly with recruiting facilities is not always possible. Objective: Obtaining the views and experiences of sperm donors regarding health and genetic matters. Design: Online survey. Setting: Not applicable. Participants: 164 previous sperm donors. Interventions: Not applicable. Main outcome measures: Views and experiences on health and genetic issues. Results: A variety of approaches are adopted by recruiting facilities in regard to selection and post-donation factors. The vast majority of donors said they had not been contacted by the facility they donated at to update their medical information, while almost one quarter of donors indicated that a health or genetic risk factor had occurred. A great majority of donors felt that they had not received any education or counselling on the potential curiosities of donor conceived people. Donors sought to be honest and open with staff but often found there were difficulties in doing so. Conclusions: Overall, donors indicate that they see donating as involving responsibilities to the offspring and families. The study highlights however that their ability to act responsibly is limited by some of the interactions or lack of them with the facilities where they donated. Implications for recruiting facilities need to be considered.
The origins of the trypanosome genome strains Trypanosoma brucei brucei TREU 927, T. b. gambiense DAL 972, T. vivax Y486 and T. congolense IL3000
Wendy Gibson
Parasites & Vectors , 2012, DOI: 10.1186/1756-3305-5-71
Abstract: The genome sequence of Trypanosoma brucei brucei TREU 927/4 was published in 2005 [1] and that of T. b. gambiense Dal 972 clone 1 in 2010 [2]. Genome sequencing projects for T. vivax Y486 and T. congolense IL3000 are also complete [3]. The trypanosome strains chosen for sequencing were selected because they had been well characterised in the laboratory, but all were isolated several decades ago (Table 1). The purpose of this short review is to provide some background information on the origins and biological characterisation of these strains as a source of reference for future users of the genome data. The history of the discovery of these trypanosome species has been recently reviewed [4].Trypanosoma brucei brucei clone TREU 927/4 was chosen as the representative T. brucei for the genome project, because it displays the full range of known phenotypes for T. brucei, barring human infectivity. TREU 927/4 is capable of complete cyclical development within the tsetse fly, including mating [5] and produces short stumpy forms during bloodstream infection in the mammalian host [6]. TREU 927/4 is a clone derived from the isolate GPAL/KE/70/EATRO 1534 [5] that originates from Kiboko, Kenya, an area where human trypanosomiasis is unknown [7]. Nevertheless, there is some doubt about the status of TREU 927/4 with regard to human infectivity, since it has a degree of resistance to human serum [8], though it lacks the SRA gene that is characteristic of the human infective subspecies T. b. rhodesiense from East Africa [9].The isolate GPAL/KE/70/EATRO 1534 was one of a collection of 15 T. brucei subgroup isolates obtained from wild caught tsetse flies of the species Glossina pallidipes from Kiboko, Kenya [7,10,11]. Each isolate was derived from the metacyclic population of a single infected fly by inoculation of macerated salivary glands into rodents; the bloodstream forms were subsequently used to study the antigenic types circulating in wild-caught flies [11]. Like other pleomor
Engagement in contemporary practice: a relational ethics perspective
Austin, Wendy;
Texto & Contexto - Enfermagem , 2006, DOI: 10.1590/S0104-07072006000500015
Abstract: the challenges and constraints of meaningful engagement with patients are discussed from a standpoint of relational ethics. if openness to others and to their situation is the beginning of ethics, as is argued by philosophers whose work informs relational ethics, then in health care we must address that openness (or its lack) as it is lived by individual health professionals within the immediacy and complexity of their practice. if, as has been also argued, disengagement is the source of maleficence within healthcare systems, addressing constraints to engagement becomes particularly urgent.
Spatial distribution of heavy metals in sediments from the Gulf of Paria,Trinidad
Revista de Biología Tropical , 2005,
Abstract: the gulf of paria receives heavy metal input from urban runoff,industrial and agricultural activity, sewage and domestic wastes:both from the west coast and from inland areas of trinidad.non-residual concentrations of nine metals,as well as total mercury concentrations,were used to determine spatial distributions of heavy metals in sediments in the gulf of paria.surficial sediment samples were collected at 37 stations,which included the mouths of 11 major rivers that flow into the gulf of paria.stations were sampled twice during the wet season (july 1998 and november/december 1998)and twice during the dry season (march 1999 and april 1999).sediments were analyzed for aluminium (al),cadmium (cd),chromium (cr),copper (cu),iron (fe), lead (pb),manganese (mn),nickel (ni),zinc (zn)and mercury (hg).total organic carbon (toc)and grain size analyses were also performed on the sediments.principal component analysis showed that sediments from river mouths subject to greatest land use and anthropogenic input,were distinct from other sediments in the gulf of paria.this was due to higher pb,zn,cu and hg concentrations (3.53-73.30 μg g-1 ,45.8-313.9 μg g-1 ,8.43-39.71 μg g-1 and 0.03-0.10 μg g-1 ,respectively).sediments further from the coast were also distinct due to their higher al,fe,cr and mn concentrations (1.37-3.16 mg g-1 ,9.51-18.91 mg g-1 ,17.22-28.41 μg g-1 and 323.6 -1,564.2 μg g-1 ,respectively).cd and pb were higher in the wet season while ni was higher in the dry season.pb,zn,cu and hg were correlated with each other and with toc.correlation was also observed between al,fe,cr,mn and ni.al,fe,cr and mn were correlated with percentage clay in sediments.the results suggest that pb,zn, cu and hg are preferentially removed by organic matter,which settles at the river-mouths,while al,fe,cr,mn, and ni become associated with clay minerals and are transported away from the coast.
Choreography and Ceremony: The Artful Side of Action
Wendy James
Human Affairs , 2007, DOI: 10.2478/v10023-007-0012-y
Abstract: "Actions" are normally thought of as taken by individuals. But to understand their quality, it is not enough to classify them from the perspective of individual psychology (rational vs. emotional, technical vs. artistic, etc.). We need to grasp their relation to those forms of collective life which have a historical existence independent of specific individual action (institutions, the conventions of social gathering, the organizing principles of games, architecture, music, ritual, etc.). This paper focuses on what characteristics such forms of collective life share, not what seems to separate them (eg. into sacred vs secular, technology vs creative art). The main features emphasized are their choreography, that is their enactment within commonly understood patterns of a spatial and temporal kind, as well as rules of interactive movement; and their ceremonial character, something which can be found in simple situations such as a conversation or a meal, though much more intensely in major religious ritual. A particularly resonant image for these enactments of social life is the dance. Because there is a ceremonial aspect to all social interaction, the paper argues that individual action, necessarily oriented to the social context, always has an "artful" side (however habitual or technical). The paper draws on the writings of Wittgenstein on action, and those of Collingwood on language and art, to shape the argument. Illustrations are provided of the "artful" employment of language (especially by actors on the stage), the "artful" side of material culture, and from the author's own ethnographic studies, the significance of dance among Sudanese refugees in Ethiopia.
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