Sample records for clinically relevant candida

  1. Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species. (United States)

    Correia, Amabel Fernandes; Silveira, Dâmaris; Fonseca-Bazzo, Yris Maria; Magalhães, Pérola Oliveira; Fagg, Christopher William; da Silva, Elton Clementino; Gomes, Suelí Maria; Gandolfi, Lenora; Pratesi, Riccardo; de Medeiros Nóbrega, Yanna Karla


    Medicinal plants have traditionally been used in many parts of the world as alternative medicine. Many extracts and essential oils isolated from plants have disclosed biological activity, justifying the investigation of their potential antimicrobial activity. In this study, the in vitro antifungal activity of six Brazilian Cerrado medicinal plant species were evaluated against clinically relevant Candida species. The crude extract plants were evaluated against American Type Culture Collection (ATCC) standard strains of Candida spp. using disk diffusion method and determining the minimum inhibitory concentration (MIC). The chemical study results were confirmed by HPLC method. All six plant species showed antifungal activity. Among the species studied, Eugenia dysenterica and Pouteria ramiflora showed significant inhibitory activity against C. tropicalis at lowest MIC value of 125 and 500 μg/disc, respectively. The Eugenia dysenterica also disclosed MIC value of 125 μg/disc against C. famata, 250 μg/disc against C. krusei and 500 μg/disc against C. guilliermondii and C. parapsilosis. Pouteria torta, Bauhinia rufa, Erythroxylum daphnites and Erythroxylum subrotundum showed activity against the yeast strains with MIC value of 1000 μg/disc. The chemical study of the most bioactive extracts of Eugenia dysenterica and Pouteria ramiflora revealed catechin derivatives and flavonoids as main components. All six evaluated plant species showed good antifungal potential against several Candida strains. However, E .dysenterica and P. ramiflora showed the higher inhibitory effect against the non-albicans Candida species. Our results may contribute to the continuing search of new natural occurring products with antifungal activity.

  2. [The relevance of Candida spp. in chronic periodontal disease]. (United States)

    Razina, I N; Chesnokova, M G; Nedoseko, V B

    The aim of the study was to assess the correlation of Candida spp. incidence in periodontal tissues with various clinical manifestations of chronic periodontal disease (CPD). Ninety patients with CPD were included in the study in which Candida spp. was evaluated in periodontal pockets content and gingival biopsy material. In severe CPD more Candida spp. were seen in gingival biopsy than in periodontal pockets (p=0.0006). Candida spp. incidence and quantity correlated directly with the disease grade showing incidence increase from 40 to 73.3% and quantity increase from 0.8±0.18 до 3.6±0.49 lg CFU/ml in light and severe CPD, correspondingly Candida spp. had statistically significant association with cyanotic gingival color (p=0.0018), tongue plaque and swelling (р=0.0042), lip exfoliation (р=0.0030), periodontal pockets depth >5 mm (р=0.0030), oral mucosa hyperemia (р=0.0157), alveolar bone destruction >1/2 of root length (р=0.0157). These data prove the relevance of Candida spp. and mycological assessment of gingival biopsy in CPD patients.

  3. Clinical Relevance of Adipokines

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    Matthias Blüher


    Full Text Available The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines changes towards a pro-inflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity, chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and its related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases.

  4. Clinical Patterns of Candida Infections in Bombay

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    J Pratiba Dalal


    Full Text Available One hundred consecutive cases of candidiasis in Bombay were studied. In each case the suspicion was confirmed by isolation typing of the Candida species. The clinical was as follows: vulvo-vaginitis 30%; intertrigo 18%; onychia and paronychia 12%; thrush 16%; generalised cutaneous candidasis 8%, enteritis 3%; bronchitis 12% and urinary tract infection 1%. When compared to a study carried out in Bombay in 1966, there was an increase in the frequency of disseminated cutaneous candidiasis and a reduction in the cases of intertrigo and onychia and paronychia.

  5. Emerging azole resistance among Candida albicans from clinical ...

    African Journals Online (AJOL)

    Candida albicans is one of the most frequently isolated yeasts in clinical laboratories and accounts for up to 80 % of the yeasts recovered from sites of infection. The study was set out to determine antifungal susceptibility of clinical isolates of Candida albicans and to establish the Minimum Inhibitory Concentrations (MIC) to ...

  6. [Presumptive identification of Candida spp. and other clinically important yeasts: usefulness of Brilliance Candida Agar]. (United States)

    Alfonso, Claudia; López, Mónica; Arechavala, Alicia; Perrone, María Del Carmen; Guelfand, Liliana; Bianchi, Mario


    Fungal infections caused by yeasts have increased during the last decades and invasive forms represent a serious problem for human health. Candida albicans is the species most frequently isolated from clinical samples. However, other emerging yeast pathogens are increasingly responsible for mycotic infections, and some of them are resistant to some antifungal drugs. Consequently, it is necessary to have methods that can provide a rapid presumptive identification at species level. Numerous chromogenic agar media have been shown to be of value as diagnostic tools. We have compared a chromogenic medium, Brilliance Candida Agar, with CHROMagar Candida, the chromogenic medium most used in our country. A multicentre study was conducted in 16 Hospitals belonging to the Mycology Net of Buenos Aires City Government. A total of 240 yeast isolates were included in this research. The new chromogenic agar showed results very similar to those obtained with CHROMagar Candida. Copyright 2009 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  7. Azasordarins: Susceptibility of Fluconazole-Susceptible and Fluconazole-Resistant Clinical Isolates of Candida spp. to GW 471558


    Cuenca-Estrella, Manuel; Mellado, Emilia; Díaz-Guerra, Teresa M.; Monzón, Araceli; Rodríguez-Tudela, Juan L.


    The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candida spp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreased susceptibility to azoles. Candida krusei, Candida parapsilosis, Candida lusitaniae, and Candida guilliermondii are resistant to GW 471558 in vitro (MICs, >128 μg/ml).

  8. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M


    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  9. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M


    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  10. The isolation of Candida rugosa and Candida mesorugosa from clinical samples in Ghana. (United States)

    Adjapong, Gloria; Bartlett, Michael; Hale, Marie; Garrill, Ashley


    Members of the Candida rugosa species complex have been described as emerging fungal pathogens and are responsible for a growing number of Candida infections. In this communication we report the isolation of Candida rugosa and Candida mesorugosa in Ghana. To the best of our knowledge this is the first description of this species complex from a clinical setting in Africa.The isolates were identified on the basis of their rRNA gene internal transcribed spacer (ITS) sequences. For one isolate, obtained from sputum, the sequence grouped well with that of C. rugosa. Two other isolates from urine had sequences that grouped with Candida mesorugosa. Morphologically, C. rugosa formed white, wrinkled, and flat colonies on Sabouraud Dextrose Agar (SDA), whereas C. mesorugosa formed white, smooth colonies. On chromogenic medium, the isolates formed small, dry greenish-blue colonies with a pale or white border, similar to C. albicans. The C. rugosa isolate produced pseudohyphae in human serum and on CMA-Tween 80 agar. In contrast, the C. mesorugosa isolates did not generate pseudohyphae in human serum, but generated a few pseudohyphae with abundant blastoconidia on CMA-Tween 80 agar. Growth was observed at 37 °C and 42 °C but not at 45 °C.The two C. mesorugosa isolates had Minimum Inhibitory Concentrations (MICs) of 6 and 48 μg ml(-1) for fluconazole and are thus resistant. The C. rugosa isolate had an MIC of 24 μg ml(-1), indicative of resistance. All three isolates were susceptible to itraconazole and voriconazole (with respective MICs of < 0.125 μg ml(-1)). © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail:

  11. Comparison of the clinical risk factors between Candida albicans and Candida non-albicans species for bloodstream infection. (United States)

    Shigemura, Katsumi; Osawa, Kayo; Jikimoto, Takumi; Yoshida, Hiroyuki; Hayama, Brian; Ohji, Goh; Iwata, Kentaro; Fujisawa, Masato; Arakawa, Soichi


    The purpose of this study is to investigate the risk factors and susceptibilities to antifungal agents of Candida albicans and Candida non-albicans species (spp.) in candidemia cases in Kobe University Hospital. We investigated all consecutive patients with candida bloodstream infection (BSI) from 2008-2013 for whose full data were available for analyses, examining clinical factors such as gender, general complications, postoperative status or susceptibilities to antifungal agents. These factors were also compared between Candida albicans spp. and Candida non-albicans by univariate and multivariate analyses. Univariate analyses showed a significantly higher rate of Candida non-albicans species BSI patients cancer (odds ratio (OR) (95% confidence interval (CI))=2.29 (1.04-5.06) and P=0.040), chemotherapy (OR=4.35 (1.11-17.1) and P=0.035), fluconazole (FLCZ) resistance (OR=77.3 (4.51-1324) and P=0.003), and itraconazole (ITCZ) resistance (OR=15.6 (5.39-45.1) and PCandida albicans. Multivariate analyses demonstrated that Candida non-albicans spp. had significantly higher rate of chemotherapy (OR=4.44 (1.04-19.0) and P=0.045), FLCZ resistance (OR=5.87 (2.01-17.1) and P=0.001), and ITCZ resistance (OR=18.7(5.77-60.4) and PCandida albicans. In conclusion, this study revealed several risk factors for BSI with Candida albicans (underlying cardiovascular diseases and postoperative status) and Candida non-albicans spp. (cancer and chemotherapy), and demonstrated that Candida non-albicans spp. were more resistant to FLCZ and ITCZ than Candida albicans.

  12. [Candida dubliniensis in clinical specimens and possibilities for identification]. (United States)

    Mahelová, M; Růžička, F


    The species Candida dubliniensis shares a wide range of phenotypic characteristics with Candida albicans, the most common yeast species isolated from clinical specimens. This is a considerable complication for the detection and identification of Candida dubliniensis from clinical specimens. The lack of data on the incidence of C. dubliniensis in the Czech Republic was the motivation behind the efforts to detect this pathogen in specimens analyzed at the Institute for Microbiology, Faculty of Medicine Masaryk University and St. Anne's Faculty Hospital in Brno. Another aim was to test the reliability of the culture methods used. Altogether 2260 yeast isolates initially identified as C. albicans were analysed. To differentiate C. dubliniensis from C. albicans, four phenotypic methods were used: colour-based differentiation on CHROMagar Candida medium, culture on medium with 6.5% of NaCl, growth at 42 °C, and colony characteristics on Staib agar. To verify the results, the Bichro-Dubli Fumouze latex agglutination test and species-specific polymerase chain reactions (PCR) were used. Using phenotypic methods, latex agglutination, and PCR, 50 (2.2%) strains from the study set were assigned to C. dubliniensis. Most (31) C. dubliniensis isolates were recovered from the respiratory tract and the remaining others were three urine isolates, four stool isolates, one central venous catheter isolate, and one blood isolate. With the exception of colour-based differentiation on CHROMagar Candida medium showing a specificity of 85.5%, all the culture methods used have a high sensitivity and a high specificity. Identification of C. dubliniensis as C. albicans was confirmed in various clinical specimens, most often from the upper respiratory tract. The colour-based differentiation of C. dubliniensis from C. albicans on chromogenic CHROMagar Candida medium can only be recommended as a screening test for the differentiation of C. dubliniensis from other species of the genus Candida

  13. An Update on Candida tropicalis Based on Basic and Clinical Approaches (United States)

    Zuza-Alves, Diana L.; Silva-Rocha, Walicyranison P.; Chaves, Guilherme M.


    Candida tropicalis has emerged as one of the most important Candida species. It has been widely considered the second most virulent Candida species, only preceded by C. albicans. Besides, this species has been recognized as a very strong biofilm producer, surpassing C. albicans in most of the studies. In addition, it produces a wide range of other virulence factors, including: adhesion to buccal epithelial and endothelial cells; the secretion of lytic enzymes, such as proteinases, phospholipases, and hemolysins, bud-to-hyphae transition (also called morphogenesis) and the phenomenon called phenotypic switching. This is a species very closely related to C. albicans and has been easily identified with both phenotypic and molecular methods. In addition, no cryptic sibling species were yet described in the literature, what is contradictory to some other medically important Candida species. C. tropicalis is a clinically relevant species and may be the second or third etiological agent of candidemia, specifically in Latin American countries and Asia. Antifungal resistance to the azoles, polyenes, and echinocandins has already been described. Apart from all these characteristics, C. tropicalis has been considered an osmotolerant microorganism and this ability to survive to high salt concentration may be important for fungal persistence in saline environments. This physiological characteristic makes this species suitable for use in biotechnology processes. Here we describe an update of C. tropicalis, focusing on all these previously mentioned subjects. PMID:29081766

  14. Functionally Relevant Residues of Cdr1p: A Multidrug ABC Transporter of Human Pathogenic Candida albicans

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    Rajendra Prasad


    Full Text Available Reduced intracellular accumulation of drugs (due to rapid efflux mediated by the efflux pump proteins belonging to ABC (ATP Binding Cassette and MFS (Major Facilitators superfamily is one of the most common strategies adopted by multidrug resistance (MDR pathogenic yeasts. To combat MDR, it is essential to understand the structure and function of these transporters so that inhibitors/modulators to these can be developed. The sequence alignments of the ABC transporters reveal selective divergence within much conserved domains of Nucleotide-Binding Domains (NBDs which is unique to all fungal transporters. Recently, the role of conserved but divergent residues of Candida Drug Resistance 1 (CDR1, an ABC drug transporter of human pathogenic Candida albicans, has been examined with regard to ATP binding and hydrolysis. In this paper, we focus on some of the recent advances on the relevance of divergent and conserved amino acids of CaCdr1p and also discuss as to how drug interacts with Trans Membrane Domains (TMDs residues for its extrusion from MDR cells.

  15. Species identification of Candida isolated from clinical specimens in a tertiary care hospital

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    lsmet Nigar


    Full Text Available Background: Candida species are responsible for various clinical manifestations from mucocutaneous overgrowth to blood stream infections especially in immunocompromized situations. Although C. albicans is the most prevalent species, high incidence of non-albicans Candida species with antifungal resistance are emerging which is posing a serious threat to the patients care.Objective: This study aimed to isolate and identify different species of Candida from different clinical specimens. Methods: A total of 100 different clinical specimens were studied of which 35 were oral swab, 28 were high vaginal swab, 15 were urine, 14 were nail, 04 were bronchoalveolar lavage and peritoneal fluid were 04. Among 100 clinical specimens, Candida isolates were identified in 64 specimens. Isolation of Candida species was done by primary culture in SDA. Subsequent identification of species were performed by germ tube test, subculture in chromo­genic agar medium and carbohydrate assimilation test with commonly used twelve sugars.Results: Out of 64 isolated Candida species, Candida albicans were 51.56% and the non-albicans Candida species were 48.44%. The most prevalent Candida species was C. albicans 33 (51.53% followed by C. tropicalis 17 (26.56%. C. glabrata 4 (6.25%, C. parapsilo­sis 4 (6.25%, C. krusei 3 (4.68% and C. guilliermondii 2 (3.2%. One of the isolated Candida species was unidentified.Conclusion: Though Candida albicans was found as the most common species, but non-albicans Candida species are appearing as emerging pathogens as well. Exposure to chemotherapy appeared to be the commonest predisposing factor for Candida infection followed by indwelling urinary catheter in situ for prolong period.



    Mohan; Ram Murugan


    BJECTIVES 1. To evaluate the Vitek 2 system for clinical identification of Candida species and their antifungal susceptibility test; 2. To study the incidence of various types of Candida species in this part of Tamilnadu. METHODS Samples collected from different wards were subjected for culture, isolation and identification of Candida Species and Antifungal Susceptibility testing by Vitek System. Vitek 2 test was carried out in Apollo Specialty Hospital Lab Services, Madurai....

  17. Comparison of the VITEK 2 antifungal susceptibility system with Etest using clinical isolates of Candida species. (United States)

    Alfouzan, Wadha; Al-Enezi, Tahani; AlRoomi, Ebteehal; Sandhya, Vayalil; Chandy, Rachel; Khan, Zia Uddin

    Candida species are part of the normal human microbiota. However, in recent years, nosocomial bloodstream Candida infections have emerged as a significant problem ranking the fourth common cause of fungemia in intensive care units. Although microdilution methods are the ones recommended for susceptibility testing, they are difficult to undertake in the clinical practice. Thus, an automated commercially available test is ideal. To compare minimum inhibitory concentrations (MICs) obtained with the recently introduced Vitek 2 yeast susceptibility system card (AST-YS01) with Etest. 263 clinical Candida isolates representing six species were included in the study. Categorical agreements (CA) were assessed as described elsewhere. Irrespective of the Candida species tested, the overall CA between Vitek 2 and Etest ranged between 66.7% and 100%. In general, Etest yielded lower MICs than Vitek 2. For Candida albicans, the CA between Vitek 2 and Etest was >95% for amphotericin B, voriconazole and flucytosine, but only 89% for fluconazole. With respect to Candida glabrata, the CA was between 97% and 100%. The major errors were with Candida krusei and flucytosine and Candida kefyr and amphotericin B. Candida tropicalis susceptibility for fluconazole by Vitek 2 reported more SDD and resistant strains than Etest. Candida parapsilosis showed 100% CA against all the four antifungals tested. No very major errors were detected between the two methods. Vitek 2 provided comparable results to Etest with quick turnaround for the testing of Candida species susceptibilities. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Antifungal potential of eugenyl acetate against clinical isolates of Candida species. (United States)

    Musthafa, Khadar Syed; Hmoteh, Jutharat; Thamjarungwong, Benjamas; Voravuthikunchai, Supayang Piyawan


    The study evaluated the efficiency of eugenyl acetate (EA), a phytochemical in clove essential oil, against clinical isolates of Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. Minimum inhibitory concentrations (MIC) of EA against Candida isolates were in the range between 0.1% and 0.4% (v/v). Spot assay further confirmed the susceptibility of Candida isolates to the compound upon treatment with respective 1 × MIC. Growth profile measured in time kill study evidence that the compound at 1 × MIC and 1/2 × MIC retarded the growth of Candida cells, divulging the fungicidal activity. Light microscopic observation demonstrated that upon treated with EA, rough cell morphology, cell damage, and fragmented patterns were observed in C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. Furthermore, unusual morphological changes of the organism were observed in scanning electron microscopic study. Therefore, it is validated that the compound could cause cell damage resulting in the cell death of Candida clinical isolates. Eventually, the compound at sub-MIC (0.0125% v/v) significantly inhibited serum-induced germ tube formation by C. albicans. Eugenyl acetate inhibited biofilm forming ability of the organisms as well as reduced the adherence of Candida cells to HaCaT keratinocytes cells. In addition, upon treatment with EA, the phagocytic activity of macrophages was increased significantly against C. albicans (P Candida infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Clinical Appearance of Oral Candida Infection and Therapeutic Strategies


    Patil, Shankargouda; Rao, Roopa S.; Majumdar, Barnali; Anil, Sukumaran


    Candida species present both as commensals and opportunistic pathogens of the oral cavity. For decades, it has enthralled the clinicians to investigate its pathogenicity and to improvise newer therapeutic regimens based on the updated molecular research. Candida is readily isolated from the oral cavity, but simple carriage does not predictably result in development of an infection. Whether it remains as a commensal, or transmutes into a pathogen, is usually determined by pre-existing or assoc...

  20. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains. (United States)

    Popp, Christina; Hampe, Irene A I; Hertlein, Tobias; Ohlsen, Knut; Rogers, P David; Morschhäuser, Joachim


    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host. Copyright © 2017 American Society for Microbiology.

  1. Clinical appearance of oral candida infection and therapeutic strategies

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    Shankargouda ePatil


    Full Text Available Candida species present both as commensals and opportunistic pathogens of the oral cavity. For decades, it has enthralled the clinicians to investigate its pathogenicity and to improvise newer therapeutic regimens based on the updated molecular research. Candida is readily isolated from the oral cavity, but simple carriage does not predictably result in development of an infection. Whether it remains as a commensal, or transmutes into a pathogen, is usually determined by pre-existing or associated variations in the host immune system. The candida infections may range from non-life threatening superficial mucocutaneous disorders to invasive disseminated disease involving multiple organs. In fact, with the increase in number of AIDS cases, there is a resurgence of less common forms of oral candida infections. The treatment after confirmation of the diagnosis should include recognizing and eliminating the underlying causes such as ill-fitting oral appliances, history of medications (antibiotics, corticosteroids, etc., immunological and endocrine disorders, nutritional deficiency states and prolonged hospitalization. Treatment with appropriate topical antifungal agents such as amphotericin, nystatin or miconazole usually resolves the symptoms of superficial infection. Occasionally, administration of systemic antifungal agents may be necessary in immunocompromised patients, the selection of which should be based upon history of recent azole exposure, a history of intolerance to an antifungal agent, the dominant Candida species and current susceptibility data.

  2. Influence of culture conditions for clinically isolated non-albicans Candida biofilm formation. (United States)

    Tan, Yulong; Leonhard, Matthias; Ma, Su; Schneider-Stickler, Berit


    Non-albicans Candida species have been isolated in increasing numbers in patients. Moreover, they are adept at forming biofilms. This study analyzed biofilm formation of clinically isolated non-albicans Candida, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, YPD and BHI) and several culture variables (inoculum concentration, incubation period and feeding conditions). The results showed that culture conditions strongly influenced non-albicans Candida species biofilm formation. YPD and BHI resulted in larger amount of biofilm formation with higher metabolic activity of biofilms. Furthermore, the growth media seems to have varying effects on adhesion and biofilm development. Growth conditions may also influence biofilm formation, which was enhanced when starting the culture with a larger inoculum, longer incubation period and using a fed-batch system. Therefore, the potential influences of external environmental factors should be considered when studying the non-albicans Candida biofilms in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. [Clinical features of invasive candidiasis and risk factors for Candida bloodstream infection in children: a multicenter study in Urumqi, China]. (United States)

    Ai Er Ken, Ai Bi Bai; Ma, Zhi-Hua; Xiong, Dai-Qin; Xu, Pei-Ru


    To investigate the clinical features of invasive candidiasis in children and the risk factors for Candida bloodstream infection. A retrospective study was performed on 134 children with invasive candidiasis and hospitalized in 5 tertiary hospitals in Urumqi, China, between January 2010 and December 2015. The Candida species distribution was investigated. The clinical data were compared between the patients with and without Candida bloodstream infection. The risk factors for Candida bloodstream infection were investigated using multivariate logistic regression analysis. A total of 134 Candida strains were isolated from 134 children with invasive candidiasis, and non-albicans Candida (NAC) accounted for 53.0%. The incidence of invasive candidiasis in the PICU and other pediatric wards were 41.8% and 48.5% respectively. Sixty-eight patients (50.7%) had Candida bloodstream infection, and 45 patients (33.6%) had Candida urinary tract infection. There were significant differences in age, rate of use of broad-spectrum antibiotics, and incidence rates of chronic renal insufficiency, heart failure, urinary catheterization, and NAC infection between the patients with and without Candida bloodstream infection (Pcandidiasis is similar between the PICU and other pediatric wards. NAC is the most common species of invasive candidiasis. Candida bloodstream infection is the most common invasive infection. Younger age (1-24 months) and NAC infection are the risk factors for Candida bloodstream infection.

  4. Women with epilepsy: clinically relevant issues


    Bangar, Santosh; Shastri, Abhishek; El-Sayeh, Hany; Cavanna, Andrea E.


    Women with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (includi...

  5. Valerian: No Evidence for Clinically Relevant Interactions

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    Olaf Kelber


    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  6. Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates.


    Baumgartner, C; Freydiere, A. M.; Gille, Y.


    Two chromogenic media, Albicans ID and CHROMagar Candida agar plates, were compared with a reference medium, Sabouraud-chloramphenicol agar, and standard methods for the identification of yeast species. This study involved 951 clinical specimens. The detection rates for the two chromogenic media for polymicrobial specimens were 20% higher than that for the Sabouraud-chloramphenicol agar plates. The rates of identification of Candida albicans for Albicans ID and CHROMagar Candida agar plates w...

  7. Clinical embryology teaching: is it relevant anymore? (United States)

    Scott, Karen M; Charles, Antony Robert; Holland, Andrew J A


    Embryology finds itself jostling for precious space in the crowded medical curriculum, yet remains important for helping students understand birth defects. It has been suggested that teaching embryology through clinical scenarios can increase its relevance and interest. The aim of this research was to determine the attitudes of final-year medical students to learning embryology and whether clinical scenarios aid understanding. Final-year medical students undertaking their paediatric rotation in 2009 and 2010 were invited to attend an optional lecture on clinical embryology and participate in the research. In the lecture, three clinical scenarios were presented, in which the lecturer traced the normal development of a foetus and the abnormal development that resulted in a birth defect. Outcomes were assessed quantitatively using a paper-based survey. The vast majority of students who valued embryology teaching in their medical programme thought it would assist them with clinical management, and believed learning through case scenarios helped their understanding. Students were divided in their beliefs about when embryology should be taught in the medical programme and whether it would increase their workload. Embryology teaching appears to be a valuable part of the medical curriculum. Embryology teaching was valued when taught in the clinical environment in later years of the medical programme. Students, clinicians and medical educators should be proactive in finding clinical learning opportunities for embryology teaching. © 2013 Royal Australasian College of Surgeons.

  8. Application of MALDI-TOF MS for requalification of a Candida clinical isolates culture collection

    Directory of Open Access Journals (Sweden)

    Reginaldo Lima-Neto


    Full Text Available Microbial culture collections underpin biotechnology applications and are important resources for clinical microbiology by supplying reference strains and/or performing microbial identifications as a service. Proteomic profiles by MALDI-TOF MS have been used for Candida spp. identification in clinical laboratories and demonstrated to be a fast and reliable technique for the routine identification of pathogenic yeasts. The main aim of this study was to apply MALDI-TOF MS combined with classical phenotypic and molecular approaches to identify Candida clinical isolates preserved from 1 up to 52 years in a Brazilian culture collection and assess its value for the identification of yeasts preserved in this type of collections. Forty Candida spp. clinical isolates were identified by morphological and biochemical analyses. Identifications were also performed by the new proteomic approach based on MALDI-TOF MS. Results demonstrated 15% discordance when compared with morphological and biochemical analyses. Discordant isolates were analysed by ITS sequencing, which confirmed the MALDI-TOF MS identifications and these strains were renamed in the culture collection catalogue. In conclusion, proteomic profiles by MALDI-TOF MS represents a rapid and reliable method for identifying clinical Candida species preserved in culture collections and may present clear benefits when compared with the performance of existing daily routine methods applied at health centres and hospitals.

  9. Application of MALDI-TOF MS for requalification of a Candida clinical isolates culture collection. (United States)

    Lima-Neto, Reginaldo; Santos, Cledir; Lima, Nelson; Sampaio, Paula; Pais, Célia; Neves, Rejane P


    Microbial culture collections underpin biotechnology applications and are important resources for clinical microbiology by supplying reference strains and/or performing microbial identifications as a service. Proteomic profiles by MALDI-TOF MS have been used for Candida spp. identification in clinical laboratories and demonstrated to be a fast and reliable technique for the routine identification of pathogenic yeasts. The main aim of this study was to apply MALDI-TOF MS combined with classical phenotypic and molecular approaches to identify Candida clinical isolates preserved from 1 up to 52 years in a Brazilian culture collection and assess its value for the identification of yeasts preserved in this type of collections. Forty Candida spp. clinical isolates were identified by morphological and biochemical analyses. Identifications were also performed by the new proteomic approach based on MALDI-TOF MS. Results demonstrated 15% discordance when compared with morphological and biochemical analyses. Discordant isolates were analysed by ITS sequencing, which confirmed the MALDI-TOF MS identifications and these strains were renamed in the culture collection catalogue. In conclusion, proteomic profiles by MALDI-TOF MS represents a rapid and reliable method for identifying clinical Candida species preserved in culture collections and may present clear benefits when compared with the performance of existing daily routine methods applied at health centres and hospitals.

  10. Identification of Candida species in the clinical laboratory: a review of conventional, commercial, and molecular techniques. (United States)

    Neppelenbroek, K H; Seó, R S; Urban, V M; Silva, S; Dovigo, L N; Jorge, J H; Campanha, N H


    In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so-called non-albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time-consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Molecular Tools for Cryptic "Candida" Species Identification with Applications in a Clinical Laboratory (United States)

    Gamarra, Soledad; Dudiuk, Catiana; Mancilla, Estefania; Vera Garate, Maria Veronica; Guerrero, Sergio; Garcia-Effron, Guillermo


    "Candida" spp. includes more than 160 species but only 20 species pose clinical problems. "C. albicans" and "C. parapsilosis" account for more than 75% of all the fungemias worldwide. In 1995 and 2005, one "C. albicans" and two "C. parapsilosis"-related species were described, respectively. Using…

  12. [Clinical relevance of cardiopulmonary reflexes in anesthesiology]. (United States)

    Guerri-Guttenberg, R A; Siaba-Serrate, F; Cacheiro, F J


    The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge reflexes and their interaction with local mechanisms, are a demonstration of the richness of cardiovascular responses that occur in human beings. As well as these, the anesthesiologist must contend with other variables that interact by attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs, surgical manipulation, and patient positioning. In the present article we review these reflexes and their clinical relevance in anesthesiology. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  13. Synergistic anticandidal activity of menthol in combination with itraconazole and nystatin against clinical Candida glabrata and Candida krusei isolates. (United States)

    Sharifzadeh, Aghil; Khosravi, Ali Reza; Shokri, Hojjatollah; Tari, Paria Samadi


    Candida glabrata (C. glabrata) and C. krusei are now emerging as serious hospital acquired infections in immunocompromised patients. Menthol, a terpenic compound, has been reported to have antifungal activity. The aim of this study was to investigate the effect of menthol in combination with itraconazole or nystatin against C. glabrata and C. krusei isolates. The effects of menthol along with itraconazole and nystatin, were evaluated by the Clinical Laboratory Standards Institute (CLSI) M44-A and CLSI M27-A3 methods. The fractional inhibitory concentration index (FICI) was determined for menthol plus itraconazole and nystatin combinations using the checkerboard method. The mean of minimum inhibitory concentration (MIC) values of menthol, nystatin and itraconazole were 53.2, 2.30 and 1.50 μg/ml for C. glabrata isolates and 121, 1.08 and 0.38 μg/ml for C. krusei isolates, respectively. Menthol in combination with itraconazole or nystatin exhibited the synergistic effects against all species of Candida tested. FICI values for menthol plus itraconazole and nystatin combinations ranged from 0.250 to 0.561 and 0.139 to 0.623 for C. glabrata isolates, and 0.182 to 0.750 and 0.188 to 0.760 for C. krusei, respectively. These results support the potential use of menthol as an anticandidal agent, and it can be used complementarily with other conventional antifungal agents. Copyright © 2017. Published by Elsevier Ltd.

  14. The clinical relevance of Tarlov cysts. (United States)

    Langdown, Andrew John; Grundy, Julian R B; Birch, Nicholas C


    The sacral perineural cyst was first described by Tarlov in 1938 as an incidental finding at autopsy. There are very few data in the literature regarding the role of Tarlov cysts in causing symptoms, however. Most studies report low numbers, and consequently, the recommendations for treatment are vague. Our aim, therefore, is to present further detail regarding the clinical relevance of Tarlov cysts and to identify whether or not they are a cause of lumbosacral spinal canal stenosis symptoms. Over a 5-year period, 3535 patients underwent magnetic resonance imaging (MRI) scan for lumbosacral symptoms. Fifty-four patients were identified as having Tarlov cysts, and their clinical picture was correlated with the findings on MRI. The majority of Tarlov cysts (n = 38) cannot be held responsible for patients' symptoms and are clinically unimportant. However, we encountered several patients in whom Tarlov cysts (n = 9) occurred at the same level as another pathology. In these cases, the cyst itself did not require any specific therapy; treatment was directed at the other pathology, and uneventful symptom resolution occurred. A smaller subgroup of cysts (n = 7) are the main cause of patients' symptoms and may require specific treatment to facilitate local decompression. The majority of Tarlov cysts are incidental findings on MRI. Where confusion exists as to the clinical relevance of a Tarlov cyst, treatment of the primary pathology (ie, non-Tarlov lesion) is usually sufficient. Tarlov cysts may, however, be responsible for a patient's symptoms; possible mechanisms by which this may occur and treatment strategies are discussed.

  15. Clinical study on thermography, as modern investigation method for Candida-associated denture stomatitis. (United States)

    Iosif, Laura; Preoteasa, Cristina Teodora; Murariu-Măgureanu, Cătălina; Preoteasa, Elena


    Candida-associated denture stomatitis is an infectious inflammatory condition of the oral mucosa, with frequent recurrences. The aim of this study was to assess the use of infrared thermography as investigation method for Candida-associated denture stomatitis (as inflammatory disorder of the maxillary denture bearing area), by comparing disease and non-disease groups. An observational study was conducted on maxillary edentulous patients treated by acrylic dentures, with and without Candida-associated denture stomatitis. Diagnostic test methods used were clinical examination for denture stomatitis and conventional microbiological culture method for oral candidiasis. Thermography analysis of the maxillary denture bearing area was made using the ThermaCAM PM350 infrared camera (Inframetrics, Flir Systems) and ThermaGram Pro 95 software, data being acquired by usage of standard protocol of thermographic registrations. The sample included 52 patients, 21 with and 31 without Candida-associated denture stomatitis. The temperature of the maxillary mucosa corresponding to the denture bearing area was found to be statistically significantly higher in Candida-associated denture stomatitis (mean 36.20°C), compared to healthy oral mucosa (mean 34.85°C). The thermal threshold value of 35.44°C was identified as best differentiating a pathological from normal state of the maxillary mucosa corresponding to the denture bearing area. In conclusion, infrared thermography, a rapid non-invasive investigation method, has the premises to bring valuable data in inflammatory disorders of the maxillary denture bearing area, as Candida-associated denture stomatitis that may be used for screening, diagnostic or monitoring purposes.

  16. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang


    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  17. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. (United States)

    Wisplinghoff, Hilmar; Ebbers, Jenny; Geurtz, Lea; Stefanik, Danuta; Major, Yvette; Edmond, Michael B; Wenzel, Richard P; Seifert, Harald


    Candida spp. are among the most frequent nosocomial pathogens, contributing significantly to morbidity and mortality. Longitudinal data on the epidemiology of Candida bloodstream infections (BSIs) are still limited. Isolates and clinical data from 1218 episodes of Candida BSI were prospectively collected from patients in 52 hospitals in the USA between 1998 and 2006. Susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, voriconazole, anidulafungin, caspofungin and micafungin were determined for 1077 Candida isolates by the CLSI reference broth microdilution method using the recently published species-specific clinical breakpoints. Candida albicans was the most prevalent species (50.7%), followed by Candida parapsilosis (17.4%), Candida glabrata (16.7%) and Candida tropicalis (10.2%). The prevalence of non-albicans Candida spp. increased over time. Patients had a mean age of 51 years and a mean length of hospital stay prior to BSI of 22 days. The main underlying conditions were gastrointestinal (20.1%) and pulmonary (13.0%) diseases. Intravenous catheters (19.1%) and the urinary tract (8.0%) were the most frequently determined likely sources, whilst in the majority of patients (61.1%) no source could be identified. Overall mortality was 38.1%. Of the isolates studied, 0.8% of C. albicans, 100.0% of C. glabrata, 2.9% of C. parapsilosis and 4.9% of C. tropicalis were non-susceptible to fluconazole, and 0.6% of C. albicans, 5.0% of Candida krusei, 7.6% of C. parapsilosis and 9.8% of C. tropicalis were non-susceptible to voriconazole. All echinocandins showed good activity against most Candida spp., including the majority of C. parapsilosis isolates, but only 38.1% of C. glabrata tested susceptible to caspofungin. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  18. Characterising atypical Candida albicans clinical isolates from six third-level hospitals in Bogotá, Colombia. (United States)

    Rodríguez-Leguizamón, Giovanni; Fiori, Alessandro; López, Luisa F; Gómez, Beatriz L; Parra-Giraldo, Claudia M; Gómez-López, Arley; Suárez, Carlos F; Ceballos, Andrés; Van Dijck, Patrick; Patarroyo, Manuel A


    Candida species are the most frequently found fungal pathogens causing nosocomial disease in a hospital setting. Such species must be correctly identified to ensure that appropriate control measures are taken and that suitable treatment is given for each species. Candida albicans is causing most fungal disease burden worldwide; the challenge lies in differentiating it from emerging atypical, minor and related species such as Candida dubliniensis and Candida africana. The purpose of this study was to compare identification based on MALDI-TOF MS to standard identification systems using a set of nosocomial isolates. Eleven nosocomial samples were collected from 6 third-level hospitals in Bogotá, Colombia. All the samples were identified by combining MALDI-TOF MS with morphological characters, carbohydrate assimilation and molecular markers (D1/D2 and HWP1). The present work describes the first collection of atypical Colombian Candida clinical isolates; these were identified as Candida albicans/Candida africana by their MALDI-TOF MS profile. Phenotypical characteristics showed that they were unable to produce chlamydospores, assimilate trehalose, glucosamine, N- acetyl-glucosamine and barely grew at 42 °C, as would be expected for Candida africana. The molecular identification of the D1/D2 region of large subunit ribosomal RNA and HWP1 hyphal cell wall protein 1 sequences from these isolates was consistent with those for Candida albicans. The mass spectra obtained by MALDI-TOF MS were analysed by multi-dimensional scaling (MDS) and cluster analysis, differences being revealed between Candida albicans, Candida africana, Candida dubliniensis reference spectra and two clinical isolate groups which clustered according to the clinical setting, one of them being clearly related to C. albicans. This study highlights the importance of using MALDI-TOF MS in combination with morphology, substrate assimilation and molecular markers for characterising Candida albicans

  19. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar


    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  20. In vitro activity of econazole in comparison with three common antifungal agents against clinical Candida strains isolated from superficial infections

    National Research Council Canada - National Science Library

    Mahdi Abastabar; Tahereh Shokohi; Reyhaneh Rouhi Kord; Hamid Badali; Seyed Jamal Hashemi; Zeinab Ghasemi; Aynaz Ghojoghi; Nesa Baghi; Maryam Abdollahi; Susan Hosseinpoor


    .... Materials and Methods: In vitro susceptibility of 100 clinical Candida isolates belonging to 6 species from superficial candidiasis of Iran towards to econazole was compared with three other common antifungal agents...


    Directory of Open Access Journals (Sweden)

    A. V. Oberemko


    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  2. In vitro synergy of natamycin and voriconazole against clinical isolates ofFusarium,Candida,AspergillusandCurvulariaspp. (United States)

    Sradhanjali, Swatishree; Yein, Bandana; Sharma, Savitri; Das, Sujata


    To determine the minimum inhibitory concentrations (MICs) of voriconazole and natamycin, alone and in combination, against the clinical isolates of Fungus and to evaluate the synergy between the drugs in an experimental in vitro study. In an experimental in vitro study, clinical isolates of Fusarium , Aspergillus , Candida and Curvularia spp were maintained on Sabouraud Dextrose Agar and used for the study. The MICs of natamycin and voriconazole, used alone and in combination, were evaluated by checkerboard microdilution technique based on the standard protocol proposed by the Clinical Laboratory Standards Institute. The interactions were assessed using the fractional inhibitory concentration (FIC) Index model. Tested with all the clinical isolates, the MICs ranged between 0.125 and 8 µg/mL both for natamycin and voriconazole. In descending order, maximum synergism (FIC ≤0.5) was observed in Candida spp (33.3%) followed by Curvularia spp and Fusarium spp (23.1%). Synergism was least for Aspergillus spp (22.2%). However, at 61.5% (8/13), maximum additive effect (>0.5-1) was observed in Aspergillus spp and minimum (33.3%, 2/6) in Candida spp. Indifference (FIC value >1 and≤4) was observed in 22.2% (2/9) of Aspergillus spp, 15.4% (2/13) of Fusarium spp, 33.3% (2/6) of Candida spp and 23.1% (3/13) of Curvularia spp. No cases of antagonism (FIC >4) were observed. Natamycin and voriconazole in combination demonstrated more effective antifungal activity than single-use in vitro treatment in all species tested, which implies that these combinations may be helpful in treating fungal keratitis. There was no antagonism between these two drugs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. [Adhesion of clinical Candida albicans isolate to buccal epithelial cells]. (United States)

    Wellmer, A


    Mucosal adherence and germ tube formation are considered to be important virulence factors of C. albicans. Adherence is a precondition for colonisation and invasion. We investigated 11 clinical isolates (among them 5 cases recovered from oesophageal thrush) for quantification of the two characteristics and correlated the results with clinical data. Adherence was measured on buccal epithelial cells and the continuous flow culture was used for quantification of germ tube formation. Adherence of strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells than isolates from patients with heavy colonisation without signs of candidosis. Strains with stronger adherence showed a significantly faster and an increased germ tube formation in the continuous flow culture. Strains from oesophageal thrush therefore show a more marked expression of the investigated virulence factors. Therefore a good adherence is a necessity for infection of the oesophagus by C. albicans. The preferential isolation of C. albicans from oesophageal thrush (> 90%) supports this assumption.

  4. Sensitivity pattern of clinical isolates of Candida albicans from hiv ...

    African Journals Online (AJOL)

    This study was carried out to investigate the sensitivity pattern of clinical isolates of C. albicans from HIV/AIDS patients to combined P. grisea extract and tioconazole. Twenty isolates of C. albicans were obtained from high vaginal swab (HVS) from HIV/AIDS patients in Bishop Shanahan Hospital, Nsukka after their ...

  5. High throughput multiplex-PCR for direct detection and diagnosis of dermatophyte species, Candida albicans and Candida parapsilosis in clinical specimen. (United States)

    Vahidnia, Ali; Bekers, Wouter; Bliekendaal, Harry; Spaargaren, Joke


    We have developed and validated a multiplex-PCR method for detection of dermatophyte spp., Candida albicans and parapsilosis for routine diagnostics. Our m-PCR showed excellent concordance with culture results in 475 clinical samples. Through the rapid diagnosis by our m-PCR, clinicians are able to initiate adequate antimycotic therapy much earlier. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. In vitro differential activity of phospholipases and acid proteinases of clinical isolates of Candida

    Directory of Open Access Journals (Sweden)

    Aurean D'Eça Júnior


    Full Text Available INTRODUCTION: Candida yeasts are commensals; however, if the balance of normal flora is disrupted or the immune defenses are compromised, Candida species can cause disease manifestations. Several attributes contribute to the virulence and pathogenicity of Candida, including the production of extracellular hydrolytic enzymes, particularly phospholipase and proteinase. This study aimed to investigate the in vitro activity of phospholipases and acid proteinases in clinical isolates of Candida spp. METHODS: Eighty-two isolates from hospitalized patients collected from various sites of origin were analyzed. Phospholipase production was performed in egg yolk medium and the production of proteinase was verified in a medium containing bovine serum albumin. The study was performed in triplicate. RESULTS: Fifty-six (68.3% of isolates tested were phospholipase positive and 16 (44.4% were positive for proteinase activity. C. tropicalis was the species with the highest number of positive isolates for phospholipase (91.7%. Statistically significant differences were observed in relation to production of phospholipases among species (p<0,0001 and among the strains from different sites of origin (p=0.014. Regarding the production of acid protease, the isolates of C. parapsilosis tested presented a larger number of producers (69.2%. Among the species analyzed, the percentage of protease producing isolates did not differ statistically (χ2=1.9 p=0.5901 (χ2=1.9 p=0.5901. CONCLUSIONS: The majority of C. non-albicans and all C. albicans isolates were great producers of hydrolytic enzymes and, consequently, might be able to cause infection under favorable conditions.

  7. Species distribution and drug susceptibility of candida in clinical isolates from a tertiary care centre at Indore

    Directory of Open Access Journals (Sweden)

    N Pahwa


    Full Text Available Background: The incidence of fungal infections has increased significantly, contributing to morbidity and mortality. This is caused by an alarming increase in infections with multi-drug resistant bacteria leading to overuse of broad-spectrum antimicrobials, which lead to overgrowth of Candida, thus enhancing its opportunity to cause disease. Candida are major human fungal pathogens that cause both mucosal and deep tissue infections. Objective : The aim of our study was to identify the distribution of Candida species among clinical isolates and their sensitivity pattern for common antifungal drugs. Materials and Methods : Two hundred and thirty-seven different clinical isolates of Candida were collected from patients visiting to a tertiary care centre of Indore from 2010 to 2012. Identification of Candida species as well as antifungal sensitivity testing was performed with Vitek2 Compact (Biomerieux France using vitek 2 cards for identification of yeast and yeast like organisms (ID-YST cards. Antifungal susceptibility testing was performed with Vitek2 "Fungal Susceptibility Card (AST YS01 kits respectively. Results : We found that the non-albicans Candida were more prevalent than Candida albicans in paediatric (60 year patients than other age group (4-18, 19-60 years patients and also in intensive care unit (ICU patients as compared to out patient department (OPD patients. Resistance rates for amphotericin B, fluconazole, flucytosine, itraconazole, and voriconazole were 2.9%, 5.9%, 0.0%, 4.2% and 2.5%%, respectively. All the strains of C. krusei were found resistant to fluconazole with intermediate sensitivity to flucytosine. Conclusion: Species-level identification of Candida and their antifungal sensitivity testing should be performed to achieve better clinical results.

  8. Clinical relevance of Mycobacterium simiae in pulmonary samples.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Dekhuijzen, P.N.R.; Soolingen, D van


    The aim of the present study was to determine the clinical relevance of Mycobacterium simiae isolation from clinical samples. The medical files of patients in the Netherlands from whom M. simiae was isolated between 1999 and 2006 were reviewed in order to assess frequency and clinical relevance.

  9. In vitro activity of econazole in comparison with three common antifungal agents against clinical Candida strains isolated from superficial infections. (United States)

    Abastabar, M; Shokohi, T; Rouhi Kord, R; Badali, H; Hashemi, S J; Ghasemi, Z; Ghojoghi, A; Baghi, N; Abdollahi, M; Hosseinpoor, S; Rahimi, N; Seifi, Z; Gholami, S; Haghani, I; Jabari, M R; Pagheh, A


    Candida species are the most common organisms involved in superficial fungal infections, worldwide. Although econazole is among the most frequently used topical formulations for the treatment of candidiasis, no information is available regarding the susceptibility profiles of Candida species in Iran. In vitro susceptibility of 100 clinical Candida isolates belonging to 6 species from superficial candidiasis of Iran towards to econazole was compared with three other common antifungal agents including itraconazole, fluconazole, and miconazole. Minimum inhibitory concentrations (MICs) values were analyzed according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 document. All isolates were previously identified to the species level, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on ITS region. The MIC of econazole, itraconazole, miconazole, and fluconazole were within the range of 0.016-16, 0.032-16, 0.016-16, and 0.25-64 μg/ml, respectively. In general, econazole and miconazole were more active against Candida isolates, compared to the other two agents. The present study demonstrated that for Candida albicans isolates, miconazole and econazole had the best effect, but in non-albicans Candida species, itraconazole and miconazole displayed more activity than other antifungal agents.

  10. Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Kamal Uddin Zaidi


    Full Text Available This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL−1 with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL−1, respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.

  11. Dynamics of Mixed- Candida Species Biofilms in Response to Antifungals. (United States)

    Vipulanandan, G; Herrera, M; Wiederhold, N P; Li, X; Mintz, J; Wickes, B L; Kadosh, D


    Oral infections caused by Candida species, the most commonly isolated human fungal pathogen, are frequently associated with biofilms. Although Candida albicans is the predominant organism found in patients with oral thrush, a biofilm infection, there is an increasing incidence of oral colonization and infections caused by non- albicans Candida species, including C. glabrata, C. dubliniensis, and C. tropicalis, which are frequently more resistant to antifungal treatment. While single-species Candida biofilms have been well studied, considerably less is known about the dynamics of mixed- Candida species biofilms and how these dynamics are altered by antifungal treatment. To address these questions, we developed a quantitative polymerase chain reaction-based approach to determine the precise species composition of mixed- Candida species biofilms formed by clinical isolates and laboratory strains in the presence and absence of clinically relevant concentrations of 3 commonly used antifungals: fluconazole, caspofungin, and amphotericin B. In monospecies biofilms, fluconazole exposure favored growth of C. glabrata and C. tropicalis, while caspofungin generally favored significant growth of all species to a varying degree. Fluconazole was not effective against preformed mixed- Candida species biofilms while amphotericin B was potent. As a general trend, in mixed- Candida species biofilms, C. albicans lost dominance in the presence of antifungals. Interestingly, presence in mixed versus monospecies biofilms reduced susceptibility to amphotericin B for C. tropicalis and C. glabrata. Overall, our data suggest that antifungal treatment favors the growth of specific non- albicans Candida species in mixed- Candida species biofilms.

  12. Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis. (United States)

    Lichtenstern, Christoph; Herold, Christina; Mieth, Markus; Brenner, Thorsten; Decker, Sebastian; Busch, Cornelius J; Hofer, Stefan; Zimmermann, Stefan; Weigand, Markus A; Bernhard, Michael


    This single-centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28-day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida-positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy-two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida-positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients. © 2015 Blackwell Verlag GmbH.

  13. Properties and clinical relevance of osteoinductive biomaterials

    NARCIS (Netherlands)

    Habibovic, Pamela


    This thesis had two main goals: (¿) to investigate parameters influencing osteoinductive potential of biomaterials in order to unravel the mechanism underlying osteoinduction and (¿¿) to investigate performance of osteoinductive biomaterials orthotopically in order to get insight into their clinical

  14. Clinically Relevant Imaging in Tuberous Sclerosis

    Directory of Open Access Journals (Sweden)

    Rupa Radhakrishnan


    Full Text Available Tuberous sclerosis (TS, also known as Bourneville disease or Bourneville-Pringle disease, is an autosomal dominant genetic disorder classically characterized by the presence of hamartomatous growths in multiple organs. TS and tuberous sclerosis complex (TSC are different terms for the same genetic condition. Both terms describe clinical changes due to mutations involving either of the two genes named TSC1 and TSC2, which regulate cell growth. The diagnosis of TSC is established using diagnostic criteria based on clinical and imaging findings. Routine screening and surveillance of patients with TSC is needed to determine the presence and extent of organ involvement, especially the brain, kidneys, and lungs, and identify the development of associated complications. As the treatment is organ specific, imaging plays a crucial role in the management of patients with TSC.

  15. Growth of Candida albicans cells on the physiologically relevant carbon source lactate affects their recognition and phagocytosis by immune cells

    NARCIS (Netherlands)

    Ene, I.V.; Cheng, S.C.; Netea, M.G.; Brown, A.J.


    Candida albicans is a normal resident of the human gastrointestinal and urogenital tracts and also a prevalent fungal pathogen. During both commensalism and infection, it must match the immunological defenses of its host while adapting to environmental cues and the local nutrient status. C. albicans

  16. Performance of Candida ID, a New Chromogenic Medium for Presumptive Identification of Candida Species, in Comparison to CHROMagar Candida


    Willinger, Birgit; Hillowoth, Cornelia; Selitsch, Brigitte; Manafi, Mammad


    Candida ID agar allows identification of Candida albicans and differentiation of other Candida species. In comparison with CHROMagar Candida, we evaluated the performance of this medium directly from 596 clinical specimens. In particular, detection of C. albicans after 24 h of incubation was easier on Candida ID (sensitivity, 96.8%) than on CHROMagar (sensitivity, 49.6%).

  17. Hepatocellular adenoma: Classification, variants and clinical relevance. (United States)

    Bioulac-Sage, Paulette; Sempoux, Christine; Balabaud, Charles


    Hepatocellular adenomas are benign tumors with two major complications, bleeding and malignant transformation. The overall narrative of hepatocellular adenoma has evolved over time. Solitary or multiple hepatocellular developing in the normal liver of women of child bearing age exposed to oral contraceptives still represents the most frequent clinical context, however, new associations are being recognized. Hepatocellular adenoma is discovered on a background of liver diseases such as non-alcoholic steatohepatitis, vascular diseases, and alcoholic cirrhosis. Hepatocellular adenoma is also reported in men, young or older adults, and even in infants. On the morpho-molecular side, the great leap forward was the discovery that hepatocellular adenoma was not a single entity and that at least 3 different subtypes exist, with specific underlying gene mutations. These mutations affect the HNF1A gene, several genes leading to JAK/STAT3 pathway activation and the CTNNB1 gene. All of them are associated with more or less specific histopathological characteristics and can be recognized using immunohistochemistry either with specific antibodies or with surrogate markers. Liver pathologists and radiologists are the key actors in the identification of the different subtypes of hepatocellular adenoma by the recognition of their specific morphological features. The major impact of the classification of hepatocellular adenoma is to identify subjects who are at higher risk of malignant transformation. With the development of new molecular technologies, there is hope for a better understanding of the natural history of the different subtypes, and, particularly for their mechanisms of malignant transformation. Copyright © 2017. Published by Elsevier Inc.

  18. Incidence and Clinical Predictors of Ocular Candidiasis in Patients with Candida Fungemia

    Directory of Open Access Journals (Sweden)

    Ayesha Khalid


    Full Text Available Purpose. The aim of this study is to determine the incidence and the predictors of ocular candidiasis among patient with Candida fungemia. Methods. We retrospectively reviewed the charts of all patients diagnosed with candidemia at the University of Kansas Medical Center during February 2000–March 2010. Data regarding patients’ demographics, clinical characteristics, laboratory results, and ophthalmology examination findings were collected. Results. A total of 283 patients with candidemia were enrolled. The mean age (± standard deviation was 55 ± 18 years; 66% were male. The most commonly isolated Candida species were C. albicans (54%, C. parapsilosis (20%, C. glabrata (13%, and C. tropicalis (8%. Only 144 (51% patients were evaluated by ophthalmology; however, the proportion of patients who were formally evaluated by an ophthalmologist increased during the study period (9%in 2000 up to 73%in 2010; P<0.0001. Evidence of ocular candidiasis was present in 18 (12.5% patients. Visual symptoms were reported by 5 of 18 (28% patients. In multivariable analysis, no predictors of ocular candidiasis were identified. Conclusions. The incidence of ocular candidiasis among patients with fungemia remains elevated. Most patients are asymptomatic and therefore all patients with candidemia should undergo fundoscopic examination to rule out ocular involvement.

  19. Candida albicans fibrinogen binding mannoprotein: expression in clinical strains and immunogenicity in patients with candidiasis. (United States)

    Sepúlveda, P; López-Ribot, J L; Murgui, A; Cantón, E; Navarro, D; Martínez, J P


    A 58 kDa cell wall-associated fibrinogen binding mannoprotein (mp58), previously characterized by our group in a Candida albicans laboratory strain (ATCC 26555), was found to be also present in the cell wall of clinical isolates of this fungus. Most strains examined appear to have functional mp58 species, as detected by their ability to bind fibrinogen. Western immunoblot analysis, with a monovalent polyclonal antibody generated against the mp58 species from strain ATCC 26555, revealed differences in recognition patterns depending on the strain tested and the culture conditions used. Serum samples from normal and Candida infected individuals were examined for the presence of antibodies against mp58 by Western immunoblotting. None of the sera from control individuals and patients suffering from superficial candidiasis contained antibodies against mp58. However, positive reactivity with this antigen and other cell wall constituents was detected for all sera from patients with confirmed systemic candidiasis. Together, these results suggest that mp58 could play an active role during infection and may be useful as a specific antigenic marker for candidiasis.

  20. Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.

    LENUS (Irish Health Repository)


    The development of resistance to azole antifungals used in the treatment of fungal infections can be a serious medical problem. Here, we investigate the molecular mechanisms associated with reduced susceptibility to fluconazole in clinical isolates of Candida dubliniensis , showing evidence of the trailing growth phenomenon. The changes in membrane sterol composition were studied in the presence of subinhibitory fluconazole concentrations. Despite lanosterol and eburicol accumulating as the most prevalent sterols after fluconazole treatment, these ergosterol precursors still support growth of Candida isolates. The overexpression of ABC transporters was demonstrated by immunoblotting employing specific antibodies against Cdr1p and Cdr2p. The presence of a full-length 170 kDa protein Cdr1p was detected in two isolates, while a truncated form of Cdr1p with the molecular mass of 85 kDa was observed in isolate 966\\/3(2). Notably, Cdr2p was detected in this isolate, and the expression of this transporter was modulated by subinhibitory concentrations of fluconazole. These results suggest that C. dubliniensis can display the trailing growth phenomenon, and such isolates express similar molecular mechanisms like that of fluconazole-resistant isolates and can therefore be associated with recurrent infections.

  1. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz


    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  2. Identificação por PCR e sensibilidade a antifúngicos de isolados clínicos vaginais de Candida sp Identification by PCR and antifungal susceptibility of vaginal clinical Candida sp isolates

    Directory of Open Access Journals (Sweden)

    Izabel Almeida Alves


    concentration for amphotericin B ranged from 0.03µg/mL to 0.25µg/mL, for fluconazole from 0.125µg/ml to 16µg/mL and for voriconazole from 0.03µg/mL to 0.25µg/m. CONCLUSIONS: Identification at Candida species level by PCR assay could be relevant for clinical management of these infections.

  3. Quantifying the clinical relevance of a laboratory observer performance paradigm. (United States)

    Chakraborty, D P; Haygood, T M; Ryan, J; Marom, E M; Evanoff, M; McEntee, M F; Brennan, P C


    Laboratory observer performance measurements, receiver operating characteristic (ROC) and free-response ROC (FROC) differ from actual clinical interpretations in several respects, which could compromise their clinical relevance. The objective of this study was to develop a method for quantifying the clinical relevance of a laboratory paradigm and apply it to compare the ROC and FROC paradigms in a nodule detection task. The original prospective interpretations of 80 digital chest radiographs were classified by the truth panel as correct (C=1) or incorrect (C=0), depending on correlation with additional imaging, and the average of C was interpreted as the clinical figure of merit. FROC data were acquired for 21 radiologists and ROC data were inferred using the highest ratings. The areas under the ROC and alternative FROC curves were used as laboratory figures of merit. Bootstrap analysis was conducted to estimate conventional agreement measures between laboratory and clinical figures of merit. Also computed was a pseudovalue-based image-level correctness measure of the laboratory interpretations, whose association with C as measured by the area (rAUC) under an appropriately defined relevance ROC curve, is as a measure of the clinical relevance of a laboratory paradigm. Low correlations (e.g. κ=0.244) and near chance level rAUC values (e.g. 0.598), attributable to differences between the clinical and laboratory paradigms, were observed. The absolute width of the confidence interval was 0.38 for the interparadigm differences of the conventional measures and 0.14 for the difference of the rAUCs. The rAUC measure was consistent with the traditional measures but was more sensitive to the differences in clinical relevance. A new relevance ROC method for quantifying the clinical relevance of a laboratory paradigm is proposed.

  4. In vitro interactions between anidulafungin and nonsteroidal anti-inflammatory drugs on biofilms of Candida spp. (United States)

    Rosato, Antonio; Catalano, Alessia; Carocci, Alessia; Carrieri, Antonio; Carone, Addolorata; Caggiano, Giuseppina; Franchini, Carlo; Corbo, Filomena; Montagna, Maria Teresa


    Candida spp. are responsible for many biomaterial-related infections; they give rise to infective pathologies typically associated with biofilm formation. We recently reported that the echinocandin anidulafungin (ANF) showed a strong in vitro activity against both planktonic and biofilms cells. Herein, we report the antifungal activities of ANF alone and in association with some non-steroidal anti-inflammatory drugs (NSAIDs) against nine Candida strain biofilms: four Candida albicans, two Candida glabrata and three Candida guilliermondii. The activity of ANF was assessed using an in vitro microbiological model relevant for clinical practice. ANF proved oneself to be active against biofilms cells, and a clear-cut synergism was found against Candida species biofilms when ANF was used in combination with three NSAIDs: aspirin, diclofenac, ibuprofen. The positive synergism against Candida spp. of ANF in association with aspirin or the other NSAIDs proved to be a very effective antifungal treatment (FICICandida biofilm pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Claudio L. Donnici


    Full Text Available The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs, such as Candida spp. [C. albicans (two clinical isolates, C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates], Paracoccidioides brasiliensis (seven clinical isolates, Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration values were very low (from 10−6 mol mL−1 to 10−8 mol mL−1 against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50 showed that the complexes are not as toxic (IC50 values are much higher—30 to 200 fold—than MIC values. These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs.

  6. Genome comparison of Candida orthopsilosis clinical strains reveals the existence of hybrids between two distinct subspecies. (United States)

    Pryszcz, Leszek P; Németh, Tibor; Gácser, Attila; Gabaldón, Toni


    The Candida parapsilosis species complex comprises a group of emerging human pathogens of varying virulence. This complex was recently subdivided into three different species: C. parapsilosis sensu stricto, C. metapsilosis, and C. orthopsilosis. Within the latter, at least two clearly distinct subspecies seem to be present among clinical isolates (Type 1 and Type 2). To gain insight into the genomic differences between these subspecies, we undertook the sequencing of a clinical isolate classified as Type 1 and compared it with the available sequence of a Type 2 clinical strain. Unexpectedly, the analysis of the newly sequenced strain revealed a highly heterozygous genome, which we show to be the consequence of a hybridization event between both identified subspecies. This implicitly suggests that C. orthopsilosis is able to mate, a so-far unanswered question. The resulting hybrid shows a chimeric genome that maintains a similar gene dosage from both parental lineages and displays ongoing loss of heterozygosity. Several of the differences found between the gene content in both strains relate to virulent-related families, with the hybrid strain presenting a higher copy number of genes coding for efflux pumps or secreted lipases. Remarkably, two clinical strains isolated from distant geographical locations (Texas and Singapore) are descendants of the same hybrid line, raising the intriguing possibility of a relationship between the hybridization event and the global spread of a virulent clone.

  7. Prevalence and Fluconazole Susceptibility Profile of Candida spp. Clinical Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil

    Directory of Open Access Journals (Sweden)

    Athayde Neves-Junior


    Full Text Available Candidiasis has become an important concern for clinical practice, especially with the increasing incidence of immunocompromised patients. In this scenario, the development resistance to fluconazole presents a challenge for treating these opportunistic infections. The aim of this study was to evaluate some epidemiology features of Candidainfections in a Brazilian University Hospital using data, previously unavailable. We observed that 44% of the 93 clinical isolates tested, belonged to Candida albicansspecies and 56% belonged to non-Candida albicansspecies (mainly Candida tropicalis and Candida glabrata. Most strains were isolated from urine samples where C. albicans was predominantly detected. 29 strains presented a fluconazole resistance phenotype and of these, 22 were chemosensitised by FK506, a classical inhibitor of ABC transporters related to azoles resistance. These data suggest the probable role of efflux pumps in this resistance phenotype. Our study highlights the need for developing effective control measures for fungal infections, rational use of antifungal drugs and development of new molecules able to abrogate the active transport of antifungals.

  8. Advances in Candida detection platforms for clinical and point-of-care applications (United States)

    Safavieh, Mohammadali; Coarsey, Chad; Esiobu, Nwadiuto; Memic, Adnan; Vyas, Jatin Mahesh; Shafiee, Hadi; Asghar, Waseem


    Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2–4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection. PMID:27093473

  9. Budding off: bringing functional genomics to Candida albicans (United States)

    Anderson, Matthew Z.


    Candida species are the most prevalent human fungal pathogens, with Candida albicans being the most clinically relevant species. Candida albicans resides as a commensal of the human gastrointestinal tract but is a frequent cause of opportunistic mucosal and systemic infections. Investigation of C. albicans virulence has traditionally relied on candidate gene approaches, but recent advances in functional genomics have now facilitated global, unbiased studies of gene function. Such studies include comparative genomics (both between and within Candida species), analysis of total RNA expression, and regulation and delineation of protein–DNA interactions. Additionally, large collections of mutant strains have begun to aid systematic screening of clinically relevant phenotypes. Here, we will highlight the development of functional genomics in C. albicans and discuss the use of these approaches to addressing both commensalism and pathogenesis in this species. PMID:26424829

  10. A review of clinically relevant human anatomy in emergency medicine. (United States)

    Campanella, Lisa Marie; Bloch, Helen; Gang, Maureen; Rennie, William; Ort, Victoria


    The objectives of this project were to establish a practical model for the review of clinical anatomy relevant to the assessment and care of the ill and injured patient, and to design practice models for invasive procedures using human cadaver, porcine cadaver, and plastic model material. A practical course based on the human gross anatomy of the face, neck, thorax, airway, arm, and leg was designed. Regional anesthesia techniques, arthrocentesis, saphenous vein cutdown, central venous and arterial cannulation, surgical airway, thoracostomy tube placement and thoracotomy were integrated into the appropriate practice stations. A syllabus was developed. A clinically relevant, online anatomy atlas demonstrating all of the above was developed. In conclusion, an anatomy review course combining clinically relevant, human, gross anatomy and procedure practice stations was established.

  11. Synthetic Organotellurium Compounds Sensitize Drug-Resistant Candida albicans Clinical Isolates to Fluconazole. (United States)

    Reis de Sá, L F; Toledo, F T; Gonçalves, A C; Sousa, B A; Dos Santos, A A; Brasil, P F; Duarte da Silva, V A; Tessis, A C; Ramos, J A; Carvalho, M A; Lamping, E; Ferreira-Pereira, A


    Invasive Candida albicans infections are a serious health threat for immunocompromised individuals. Fluconazole is most commonly used to treat these infections, but resistance due to the overexpression of multidrug efflux pumps is of grave concern. This study evaluated the ability of five synthetic organotellurium compounds to reverse the fluconazole resistance of C. albicans clinical isolates. Compounds 1 to 4, at fluconazole resistance of Saccharomyces cerevisiae strains overexpressing the major C. albicans multidrug efflux pumps Cdr1p and Mdr1p, whereas compound 5 only sensitized Mdr1p-overexpressing strains to fluconazole. Compounds 1 to 4 also inhibited efflux of the fluorescent substrate rhodamine 6G and the ATPase activity of Cdr1p, whereas all five of compounds 1 to 5 inhibited Nile red efflux by Mdr1p. Interestingly, all five compounds demonstrated synergy with fluconazole against efflux pump-overexpressing fluconazole-resistant C. albicans clinical isolates, isolate 95-142 overexpressing CDR1 and CDR2, isolate 96-25 overexpressing MDR1 and ERG11, and isolate 12-99 overexpressing CDR1, CDR2, MDR1, and ERG11 Overall, organotellurium compounds 1 and 2 were the most promising fluconazole chemosensitizers of fluconazole-resistant C. albicans isolates. Our data suggest that these novel organotellurium compounds inhibit pump efflux by two very important and distinct families of fungal multidrug efflux pumps: the ATP-binding cassette transporter Cdr1p and the major facilitator superfamily transporter Mdr1p. Copyright © 2016 American Society for Microbiology.

  12. Characterization of Candida spp isolated from blood cultures and clinical aspects of candidemia


    Alencar, Débora de Souza Olartechea de


    O aumento de infecções invasivas por leveduras do gênero Candida representa um grave problema de saúde pública. Recentemente observa-se a emergência global de espécies de Candida não Candida albicans como agente de candidemia. Objetivou-se neste estudo descrever as características demográficas e clínicas de 32 pacientes com diagnóstico laboratorial de candidemia, identificar as espécies envolvidas e determinar o perfil de suscetibilidade aos antifúngicos. O estudo foi realizado no Hospital Un...

  13. In vitro activity of fluconazole and amphotericin B against Candida inconspicua clinical isolates as determined by the time-kill method

    DEFF Research Database (Denmark)

    Szabó, Zsuzsanna; Sóczó, Georgina; Miszti, Cecilia


    Candida inconspicua is an emerging pathogen in immunocompromised patients possessing inherently decreased susceptibility to fluconazole. We determined the MICs and killing activity of fluconazole and amphotericin B against C. inconspicua clinical isolates as well as reference strain C. inconspicu...

  14. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and Bayesian phylogenetic analysis to characterize Candida clinical isolates. (United States)

    Angeletti, Silvia; Lo Presti, Alessandra; Cella, Eleonora; Dicuonzo, Giordano; Crea, Francesca; Palazzotti, Bernardetta; Dedej, Etleva; Ciccozzi, Massimo; De Florio, Lucia


    Clinical Candida isolates from two different hospitals in Rome were identified and clustered by MALDI-TOF MS system and their origin and evolution estimated by Bayesian phylogenetic analysis. The different species of Candida were correctly identified and clustered separately, confirming the ability of these techniques to discriminate between different Candida species. Focusing MALDI-TOF analysis on a single Candida species, Candida albicans and Candida parapsilosis strains clustered differently for hospital setting as well as for period of isolation than Candida glabrata and Candida tropicalis isolates. The evolutionary rates of C. albicans and C. parapsilosis (1.93×10(-2) and 1.17×10(-2)substitutions/site/year, respectively) were in agreement with a higher rate of mutation of these species, even in a narrow period, than what was observed in C. glabrata and C. tropicalis strains (6.99×10(-4) and 7.52×10(-3)substitutions/site/year, respectively). C. albicans resulted as the species with the highest between and within clades genetic distance values in agreement with the temporal-related clustering found by MALDI-TOF and the high evolutionary rate 1.93×10(-2)substitutions/site/year. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy (United States)

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In t...

  16. Proprioceptive deficits after ACL injury : are they clinically relevant?

    NARCIS (Netherlands)

    Gokeler, Alli; Benjaminse, Anne; Hewett, Timothy E.; Lephart, Scott M.; Engebretsen, Lars; Ageberg, Eva; Engelhardt, Martin; Arnold, Markus P.; Postema, Klaas; Otten, Egbert; Dijkstra, Pieter U.

    Objective To establish the clinical relevance of proprioceptive deficits reported after anterior cruciate ligament (ACL) injury. Material and methods A literature search was done in electronic databases from January 1990 to June 2009. Inclusion criteria for studies were ACL deficient (ACL-D) and ACL

  17. Meaning in life : Clinical relevance and predictive power

    NARCIS (Netherlands)

    Debats, DL


    The clinical relevance of the meaning in life construct is examined by evaluating its ability to predict patients' general and psychological well-being and their posttreatment functioning. Evidence is obtained for the notion that meaning in Life (a) would affect both positive and negative aspects of

  18. Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage (United States)

    Blake, Margaret Lehman


    Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

  19. Candida guilliermondii: biotechnological applications, perspectives for biological control, emerging clinical importance and recent advances in genetics. (United States)

    Papon, Nicolas; Savini, Vincenzo; Lanoue, Arnaud; Simkin, Andrew J; Crèche, Joël; Giglioli-Guivarc'h, Nathalie; Clastre, Marc; Courdavault, Vincent; Sibirny, Andriy A


    Candida guilliermondii (teleomorph Meyerozyma guilliermondii) is an ascomycetous species belonging to the Saccharomycotina CTG clade which has been studied over the last 40 years due to its biotechnological interest, biological control potential and clinical importance. Such a wide range of applications in various areas of fundamental and applied scientific research has progressively made C. guilliermondii an attractive model for exploring the potential of yeast metabolic engineering as well as for elucidating new molecular events supporting pathogenicity and antifungal resistance. All these research fields now take advantage of the establishment of a useful molecular toolbox specifically dedicated to C. guilliermondii genetics including the construction of recipient strains, the development of selectable markers and reporter genes and optimization of transformation protocols. This area of study is further supported by the availability of the complete genome sequence of the reference strain ATCC 6260 and the creation of numerous databases dedicated to gene ontology annotation (metabolic pathways, virulence, and morphogenesis). These genetic tools and genomic resources represent essential prerequisites for further successful development of C. guilliermondii research in medical mycology and in biological control by facilitating the identification of the multiple factors that contribute to its pathogenic potential. These genetic and genomic advances should also expedite future practical uses of C. guilliermondii strains of biotechnological interest by opening a window into a better understanding of the biosynthetic pathways of valuable metabolites.

  20. MFS transporters of Candida species and their role in clinical drug resistance. (United States)

    K Redhu, Archana; Shah, Abdul H; Prasad, Rajendra


    ABC (ATP-binding cassette) and MFS (major facilitator superfamily) exporters, belonging to two different superfamilies, are one of the most prominent contributors of multidrug resistance (MDR) in yeast. While the role of ABC efflux pump proteins in the development of MDR is well documented, the MFS transporters which are also implicated in clinical drug resistance have not received due attention. The MFS superfamily is the largest known family of secondary active membrane carriers, and MFS exporters are capable of transporting a host of substrates ranging from small molecules, including organic and inorganic ions, to complex biomolecules, such as peptide and lipid moieties. A few of the members of the drug/H(+) antiporter family of the MFS superfamily function as multidrug transporters and employ downhill transport of protons to efflux their respective substrates. This review focuses on the recent developments in MFS of Candida and highlights their role in drug transport by using the example of the relatively well characterized promiscuous Mdr1 efflux pump of the pathogenic yeast C. albicans. © FEMS 2016. All rights reserved. For permissions, please e-mail:

  1. Progress in Antifungal Susceptibility Testing of Candida spp. by Use of Clinical and Laboratory Standards Institute Broth Microdilution Methods, 2010 to 2012 (United States)

    Pfaller, M. A.


    Antifungal susceptibility testing of Candida has been standardized and refined and now may play a useful role in managing Candida infections. Important new developments include validation of 24-h reading times for all antifungal agents and the establishment of species-specific epidemiological cutoff values (ECVs) for the systemically active antifungal agents and both common and uncommon species of Candida. The clinical breakpoints (CBPs) for fluconazole, voriconazole, and the echinocandins have been revised to provide species-specific interpretive criteria for the six most common species. The revised CBPs not only are predictive of clinical outcome but also provide a more sensitive means of identifying those strains with acquired or mutational resistance mechanisms. This brief review serves as an update on the new developments in the antifungal susceptibility testing of Candida spp. using Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) methods. PMID:22740712

  2. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth


    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  3. Yeast identification in routine clinical microbiology laboratory and its clinical relevance

    Directory of Open Access Journals (Sweden)

    S Agarwal


    Full Text Available Rapid identification of yeast infections is helpful in prompt appropriate antifungal therapy. In the present study, the usefulness of chromogenic medium, slide culture technique and Vitek2 Compact (V2C has been analysed. A total of 173 clinical isolates of yeast species were included in the study. An algorithm to identify such isolates in routine clinical microbiology laboratory was prepared and followed. Chromogenic medium was able to identify Candida albicans, C. tropicalis, C. krusei, C. parapsilosis and Trichosporon asahii. Chromogenic medium was also helpful in identifying "multi-species" yeast infections. The medium was unable to provide presumptive identification of C. pelliculosa, C. utilis, C. rugosa, C. glabrata and C. hemulonii. Vitek 2 compact (V2C differentiated all pseudohypae non-producing yeast species. The algorithm followed was helpful in timely presumptive identification and final diagnosis of yeast infections, including multi-species yeast infections.

  4. Clinical relevance of narrow-band imaging in flexible cystoscopy

    DEFF Research Database (Denmark)

    Drejer, Ditte; Béji, Sami; Munk Nielsen, Anna


    urological departments. Patients had either hematuria (n = 483) or known recurrent non-muscle-invasive bladder cancer (NMIBC) (n = 472). High-definition (HD) cystoscopy was performed in white light (WL) and a preliminary clinical decision was made. Then, a second cystoscopy was performed in NBI...... patients (3.1%) in whom a WL cystoscopy revealed no tumor. In total, NBI changed the clinical decision relevantly in 1.9% of the patients. In hematuria patients, the calculated sensitivities of both NBI and WL were identically high, whereas sensitivity in patients with known NMIBC was significantly higher...

  5. [Microscopic colitis--new insights relevant to clinical practice]. (United States)

    Miehlke, S; Aust, D; Madisch, A


    Microscopic colitis is an increasingly recognised chronic inflammatory bowel disease associated with watery, non-bloody diarrhoea. In addition, many patients suffer from abdominal pain, nocturnal diarrhoea, urgency and incontinence. The two traditional histological subtypes are collagenous colitis and lymphocytic colitis. A novel third subgroup is the so-called incomplete microscopic colitis which is clinically indistinguishable. At present, budesonide is the only evidenced-based effective therapy, however many problems in the long-term treatment strategy are still unsolved. The present paper reviews new developments in microscopic colitis which are relevant for clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Hypersusceptibility to Azole Antifungals in a Clinical Isolate of Candida glabrata with Reduced Aerobic Growth ▿ (United States)

    Vandeputte, Patrick; Tronchin, Guy; Rocher, Françoise; Renier, Gilles; Bergès, Thierry; Chabasse, Dominique; Bouchara, Jean-Philippe


    Petite mutations have been described in Saccharomyces cerevisiae and pathogenic yeasts. However, previous studies of the phenotypic traits of these petite mutants reported that they express azole resistance. We describe a clinical isolate of Candida glabrata with a striking association between increased susceptibility to azoles and respiratory deficiency. This isolate was obtained from a urine sample together with a respiration-competent C. glabrata isolate which exhibited azole resistance. The respiratory status of the two isolates was confirmed by cultivation on glycerol-containing agar and oxygraphy. Flow cytometry revealed the normal incorporation of rhodamine 123, and mitochondrial sections with typical cristae were seen by transmission electron microscopy for both isolates. Together, these results suggested a nuclear origin for the reduced respiratory capacity of the hypersusceptible isolate. The sterol contents of these isolates were similar to the sterol content of a reference strain. Sequencing of the ERG11 and PDR1 genes revealed that the sequences were identical in the two isolates, demonstrating their close relatedness. In addition to silent mutations, they carried a nonsense mutation in PDR1 that led to the truncation of transcription factor Pdr1p. They also overexpressed both PDR1 and one of its targets, CDR1, providing a possible explanation for the azole resistance of the respiration-competent isolate. In conclusion, in addition to azole resistance, which is a common feature of C. glabrata mitochondrial petite mutants, the mutation of a nuclear gene affecting aerobic growth may lead to azole hypersusceptibility; however, the mechanisms underlying this phenotype remain to be determined. PMID:19380598

  7. Molecular mechanisms associated with Fluconazole resistance in clinical Candida albicans isolates from India. (United States)

    Mane, Arati; Vidhate, Pallavi; Kusro, Chanchal; Waman, Vaishali; Saxena, Vandana; Kulkarni-Kale, Urmila; Risbud, Arun


    Resistance to azole antifungals is a significant problem in Candida albicans. An understanding of resistance at molecular level is essential for the development of strategies to tackle resistance and rationale design of newer antifungals and target-based molecular approaches. This study presents the first evaluation of molecular mechanisms associated with fluconazole resistance in clinical C.albicans isolates from India. Target site (ERG11) alterations were determined by DNA sequencing, whereas real-time PCRs were performed to quantify target and efflux pump genes (CDR1, CDR2, MDR1) in 87 [Fluconazole susceptible (n = 30), susceptible-dose dependent (n = 30) and resistant (n = 27)] C.albicans isolates. Cross-resistance to fluconazole, ketoconazole and itraconazole was observed in 74.1% isolates. Six amino acid substitutions were identified, including 4 (E116D, F145L, E226D, I437V) previously reported ones and 2 (P406L, Q474H) new ones. CDR1 over-expression was seen in 77.7% resistant isolates. CDR2 was exclusively expressed with CDR1 and their concomitant over-expression was associated with azole cross-resistance. MDR1 and ERG11 over-expression did not seem to be associated with resistance. Our results show that drug efflux mediated by Adenosine-5'-triphosphate (ATP)-binding cassette transporters, especially CDR1 is the predominant mechanism of fluconazole resistance and azole cross-resistance in C. albicans and indicate the need for research directed towards developing strategies to tackle efflux mediated resistance to salvage azoles. © 2015 Blackwell Verlag GmbH.

  8. Isolation of Candida Species from Gastroesophageal Lesions among Pediatrics in Isfahan, Iran: Identification and Antifungal Susceptibility Testing of Clinical Isolates by E-test

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    Fatemeh Salehi


    Full Text Available Background: Candida species can become opportunistic pathogens causing local or systemic invasive infections. Gastroesophageal candidiasis may depend on the Candida colonization and local damage of the mucosal barrier. Risk factors are gastric acid suppression, diabetes mellitus, chronic debilitating states such as carcinomas, and the use of systemic antibiotics and corticosteroids. The aim of this study is collection and molecular identification of Candida species from gastroesophageal lesions among pediatrics in Isfahan, and determination of minimum inhibitory concentration (MIC ranges for clinical isolates. Materials and Methods: A total of 200 patients underwent endoscopy (130 specimens from gastritis and 70 samples from esophagitis were included in this study between April 2015 and November 2015. All specimens were subcultured on sabouraud dextrose agar, and genomic DNA of all strains was extracted using boiling method. Polymerase chain reaction and DNA sequencing of the ITS1-5.8SrDNA-ITS2 region were used for the identification of all Candida strains. MIC ranges were determined for itraconazole (ITC, amphotericin B (AmB, and fluconazole (FLU by E-test. Results: Twenty of 200 suspected patients (10% were positive by direct microscopy and culture. Candida albicans was the most common species (60% followed by Candida glabrata (30%, Candida parapsilosis (5%, and Candida kefyr (5%. MIC ranges were determined for FLU (0.125–8 μg/mL, ITC (0.008–0.75 μg/mL, and AmB (0.008–0.75 μg/mL, respectively. Conclusion: Every colonization of Candida species should be considered as a potentially factor of mucocutaneous candidiasis and should be treated with antifungal drugs.

  9. Current Views on the Clinical Relevance of Blastocystis spp. (United States)

    Tan, Kevin S W; Mirza, Haris; Teo, Joshua D W; Wu, Binhui; Macary, Paul A


    Blastocystis is an enteric protistan parasite of uncertain clinical relevance. Recent studies indicate that the parasite is a species complex and humans are potentially hosts to nine Blastocystis subtypes, most of which are zoonotic. Subtype 3 is the most common in prevalence studies, followed by subtype 1. Laboratory diagnosis is challenging; the currently recommended diagnostic approach is trichrome staining of direct smears coupled with stool culture. Polymerase chain reaction testing from stools or culture is useful for determining Blastocystis subtype information. The controversial pathogenesis of Blastocystis is attributed to subtype variations in virulence; although current studies seem to support this idea, evidence suggests other factors also contribute to the clinical outcome of the infection. Clinical signs and symptoms of blastocystosis include abdominal pain, diarrhea, bloating, and flatulence. Extraintestinal manifestations, predominantly cutaneous, also were reported. In vitro and animal studies shed new light on the pathobiology of Blastocystis.

  10. Prevalence of Candida albicans and Candida dubliniensis in caries-free and caries-active children in relation to the oral microbiota-a clinical study. (United States)

    Al-Ahmad, A; Auschill, T M; Dakhel, R; Wittmer, A; Pelz, K; Heumann, C; Hellwig, E; Arweiler, N B


    The correlation between caries and the oral prevalence of Candida spp. in children is contradictory in literature. Thereby, authors focused on Candida albicans as the most isolated Candida species from the oral cavity. Therefore, the aim of the present study was to compare caries-free and caries-bearing children regarding their oral carriage of Candida spp. Twenty-six caries-free (CF group) and 26 caries-active children (CA group) were included into this study. Three different types of specimens were assessed, saliva and plaque, and in the case of caries, infected dentine samples were microbiologically analyzed for aerobic and anaerobic microorganisms and their counts. Special attention was given to the differentiation between C. albicans and Candida dubliniensis. Additionally, different biochemical tests, VITEK 2 (VITEK®2, bioMérieux, Marcy-l'Etoile, France) and 16S and 18S ribosomal DNA (rDNA) sequencing, were applied for identification. The detection of C. albicans did not differ between the CF and CA groups. C. dubliniensis was never detected in any specimen of the CF group, but occurred in one quarter of the CA group (27 % in plaque, 23 % in saliva), thus leading to a statistically significant difference between the two groups (p albicans. Microbiological diagnostic-especially of oral Candida species-is an important determinant for identifying etiological factors of dental caries in children.

  11. Oral ulcers in children under chemotherapy: clinical characteristics and their relation with Herpes Simplex Virus type 1 and Candida albicans. (United States)

    Sepúlveda, Ester; Brethauer, Ursula; Rojas, Jaime; Fernández, Eduardo; Le Fort, Patricia


    The objective of this study was to determine the clinical characteristics of oral ulcers in pediatric oncology patients undergoing chemotherapy and their relation with the presence of Herpes Simplex Virus (HSV) type 1 and Candida albicans. The sample consisted of 20 ulcerative lesions from 15 children treated with chemotherapy in the Pediatric Service of the Regional Hospital of Concepción, Chile. Two calibrated clinicians performed clinical diagnosis of the ulcers and registered general data from the patients (age, general diagnosis, absolute neutrophil count, and number of days after chemotherapy) and clinical characteristic of the ulcers: number, size, location, presence or absence of pain and inflammatory halo, edge characteristics, and exudate type. Additional to clinical diagnosis, culture for Candida albicans (C) and polymerase chain reaction (PCR) for Herpes Simplex Virus type 1 was performed. Ten ulcers occurred in patients with acute lymphoblastic leukemia, five in patients with acute myeloblastic leukemia and five in patients with other neoplastic diseases. Eight ulcers were HSV (+) / C (-), 6 HSV (-) / C (-), 4 HSV (+) / C (+) and 2 HSV (-) / C (+). Preferential location was the hard palate. Most lesions were multiple, painful, with inflammatory halo, irregular edges and fibrinous exudate. The average size was 6,5 millimeters, and the mean number of days after chemotherapy was 7.5 days. Oral ulcers in children with oncological diseases did not present a specific clinical pattern. They were strongly associated with HSV.

  12. Cyclosporine A decreases the fluconazole minimum inhibitory concentration of Candida albicans clinical isolates but not biofilm formation and cell growth. (United States)

    Wibawa, T; Nurrokhman; Baly, I; Daeli, P R; Kartasasmita, G; Wijayanti, N


    Among the genus Candida, Candida albicans is the most abundant species in humans. One of the virulent factors of C. albicans is its ability to develop biofilm. Biofilm forming microbes are characterized by decreasing of its susceptibility to antibiotics and antifungal. The fungicidal effect of fluconazole may be enhanced by cyclosporine A in laboratory engineered C. albicans strains. The aim of this work is to analyze the synergistic effect of cyclosporine A with fluconazole in C. albicans clinical isolates and the effect of cycolsporine A alone in the biofilm formation. Six fluconazole resistant and six sensitive C. albicans clinical isolates were analyzed for its minimum inhibitory concentration (MICs), biofilm formation, and cell growths. A semi-quantitative XTT [2,3-bis(2-methoxy-4-nitro-5- sulfo-phenyl)-2H-tetrazolium-5-carboxanilide] reduction assay was conducted to measure the biofilm formation. Cyclosporine A has synergistic effect with fluconazole that was shown by decreasing MICs of both fluconazole resistant and sensitive C. albicans clinical isolates. However, cyclosporine A alone did not influence the biofilm formation and cell growth of both fluconazole resistant and sensitive C. albicans clinical isolates. These results indicated that cyclosporine A might be a promising candidate of adjuvant therapy for fluconazole against both fluconazole resistant and sensitive C. albicans clinical isolates.

  13. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. (United States)

    Dinis-Oliveira, Ricardo Jorge


    Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

  14. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy. (United States)

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A


    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy).

  15. Antifungal susceptibility testing of Candida in the Clinical Laboratory: how to do it, when to do it, and how to interpret it

    Directory of Open Access Journals (Sweden)

    Esther Manso


    Full Text Available Significant changes in the management of fungaemia have occurred in the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. The emergence of drug resistance in fungal pathogens has a profound impact on human health given limited number of antifungal drugs. Antifungal resistance in Candida may be either intrinsic or acquired and may be encountered in the antifungal drug exposed but also the antifungal drug naïve patient The variation in resistance rates between centers emphasizes that it is essential to have knowledge of the local Candida species distribution and antifungal resistance rates to guide initial therapy for Candida BSI. Moreover, all Candida isolates from blood and normally sterile sites should be identified to the species level. The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing have developed breakpoints and epidemiological cutoff values that are now established for Candida spp. Clinical microbiology laboratories will be employed commercial susceptibility assays, rather than reference broth microdilution methods and comparative studies are particularly important. Vitek 2®, Etest® and Sensititre YeastOne® provided a high degree of essential agreement and comparable sensitivity and specificity to BMD-RPMI for identifying resistance to azole and echinocandins in Candida spp.

  16. Nosocomial Bloodstream Infection Due to Candida spp. in China: Species Distribution, Clinical Features, and Outcomes. (United States)

    Li, Ying; Du, Mingmei; Chen, Liang-An; Liu, Yunxi; Liang, Zhixin


    To investigate the distribution of Candida spp., predictors of mortality, and effects of therapeutic measures on outcomes of nosocomial bloodstream infection (BSI) due to Candida spp. This retrospective, population-based study enrolled adult patients with Candida nosocomial BSI from January 2010 to December 2014 in one tertiary care hospital. The demographics, comorbidities, species distribution, risk factors, and effects of antifungal treatment were assessed. In total, 190 episodes of Candida BSI were identified. The most prevalent species was C. albicans (38.9 %), followed by C. parapsilosis (23.2 %) and C. tropicalis (20.5 %). In vitro susceptibility testing showed that 88.9 % of Candida isolates were susceptible to fluconazole. The 30-day hospital mortality was 27.9 %, while the early mortality (within 7 days) was 16.3 %. In a multivariate regression analysis, the Acute Physiology and Chronic Health Evaluation II score [odds ratio (OR) 1.23; 95 % confidence interval (CI) 1.080-1.390; P = 0.002] and severe sepsis or septic shock (OR 15.35; 95 % CI 2.391-98.502; P = 0.004) were independently correlated with early mortality. Severe sepsis or septic shock (OR 24.75; 95 % CI 5.099-120.162; P risk factor for 30-day mortality, while proven catheter-related candidemia (OR 0.16; 95 % CI 0.031-0.810; P = 0.027) was a positive factor for 30-day mortality. Early central venous catheter removal and adequate antifungal treatment were closely related to decreased mortality in patients with primary candidemia. The proportion of candidemia caused by C. albicans was lower than that caused by non-albicans species. The severity of illness influenced early mortality, and the origin of the central venous catheter remarkably affected 30-day mortality.

  17. Selected Food/Herb-Drug Interactions: Mechanisms and Clinical Relevance. (United States)

    Amadi, Cecilia N; Mgbahurike, Amaka A


    Food/Herb-drug interactions have become a major problem in health care. These interactions can lead to loss of therapeutic efficacy or toxic effects of drugs. To probe the clinical relevance of such interactions, the impact of food/herb intake on the clinical effects of drug administration has to be evaluated. Failure to identify and efficiently manage food-drug interactions can lead to serious consequences. A comprehensive knowledge of the mechanisms that underpin variability in disposition will help optimize therapy. Electronic search of literatures from relevant databases were conducted. A total of 58 original scientific reports/review articles were obtained with the search strategy; of which 25 were found eligible to be included in the present review. Required data were extracted from these studies, and their methodologies were assessed. This review updates our knowledge on clinical food-drug interactions with emphasis on mechanism and clinical implications. Results obtained from literature search identified interactions with selected foods/herbs generated from in vivo and in vitro studies. For example, interaction studies in humans revealed a reduction in the bioavailability of mercaptopurine when taken concurrently with substances containing xanthine oxidase (eg, cow milk); a reduction in the bioavailability of quinine with Garcinia kola; increased bioavailability/toxicity of felodipine, nifedipine, saquinavir, sildenafil with grape juice; increased bioavailability of felodipine, cisapride with red wine and diminished bioavailability of fexofenadine with apple. Pharmacokinetic and/or pharmacodynamic mechanisms are implicated in many of these interactions. By evaluating the dietary patterns of patients and use of prescribed medications, health professionals will be well informed of potential interactions and associated adverse effects.

  18. Clinically Relevant Drug Interactions with Anti-Alzheimer's Drugs. (United States)

    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo


    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. The concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at

  19. Fluconazole resistance in Candida species: a current perspective

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    Berkow EL


    Full Text Available Elizabeth L Berkow, Shawn R Lockhart Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Candida albicans and the emerging non-albicans Candida spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections, but it is only fungistatic against Candida spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in C. albicans are also found in the non-albicans species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp., including the global health threat Candida auris, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which Candida spp. manifest resistance to it. Keywords: Candida, fluconazole resistance, ERG11, drug efflux, ergosterol

  20. In vitro activity of econazole in comparison with three common antifungal agents against clinical Candida strains isolated from superficial infections

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    Mahdi Abastabar


    Conclusion: The present study demonstrated that for Candida albicans isolates, miconazole and econazole had the best effect, but in non-albicans Candida species, itraconazole and miconazole displayed more activity than other antifungal agents.

  1. Development of clinically relevant implantable pressure sensors: perspectives and challenges. (United States)

    Clausen, Ingelin; Glott, Thomas


    This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

  2. Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

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    Ingelin Clausen


    Full Text Available This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

  3. Streptococcus pyogenes biofilms – formation, biology,and clinical relevance

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    Tomas eFiedler


    Full Text Available Streptococcus pyogenes (group A streptococci, GAS is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  4. Clinical strains of Lactobacillus reduce the filamentation of Candida albicans and protect Galleria mellonella against experimental candidiasis. (United States)

    Rossoni, Rodnei Dennis; Dos Santos Velloso, Marisol; Figueiredo, Lívia Mara Alves; Martins, Carolina Pistille; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos


    Candida albicans is the most common human fungal pathogen and can grow as yeast or filaments, depending on the environmental conditions. The filamentous form is of particular interest because it can play a direct role in adherence and pathogenicity. Therefore, the purpose of this study was to evaluate the effects of three clinical strains of Lactobacillus on C. albicans filamentation as well as their probiotic potential in pathogen-host interactions via an experimental candidiasis model study in Galleria mellonella. We used the reference strain Candida albicans ATCC 18804 and three clinical strains of Lactobacillus: L. rhamnosus strain 5.2, L. paracasei strain 20.3, and L. fermentum strain 20.4. First, the capacity of C. albicans to form hyphae was tested in vitro through association with the Lactobacillus strains. After that, we verified the ability of these strains to attenuate experimental candidiasis in a Galleria mellonella model through a survival curve assay. Regarding the filamentation assay, a significant reduction in hyphae formation of up to 57% was observed when C. albicans was incubated in the presence of the Lactobacillus strains, compared to a control group composed of only C. albicans. In addition, when the larvae were pretreated with Lactobacillus spp. prior to C. albicans infection, the survival rate of G. mellonela increased in all experimental groups. We concluded that Lactobacillus influences the growth and expression C. albicans virulence factors, which may interfere with the pathogenicity of these microorganisms.

  5. Candida vulturna pro tempore sp. nov., a dimorphic yeast species related to the Candida haemulonis species complex isolated from flowers and clinical sample. (United States)

    Sipiczki, Matthias; Tap, Ratna Mohd


    In a taxonomic study of yeasts isolated from flowers in Cagayan de Oro, Mindenao Island, The Philippines, strains were identified as representing Kabatiella microsticta, Metschnikowia koreensis and a hitherto undescribed dimorphic species. Sequences of the D1/D2 domains of the LSU 26S rRNA genes, the internal transcribed spacer (ITS) regions and the SSU 18S rRNA genes were identical in the strains of the last-named group and differed from the corresponding sequences of the type strain of the closest related species, Candida duobushaemulonii, by 4 % (D1/D2), 7 % (ITS) and 1 % (SSU). In an independent study, a strain with D1/D2 and ITS sequences very similar to those of the Philippine strains was isolated in Malaysia from the blood of a patient dying of aspiration pneumonia. Both groups of isolates were moderately sensitive to anidulafungin, caspofungin, fluconazole, itraconazole and voriconazole but resistant to amphotericin B. Molecular phylogenetic analysis of the sequences placed the Philippine and Malaysian isolates close to the Candida haemulonis complex of Candida species. To reflect the geographical location of the sites of sample collection, the novel species name Candida vulturna pro tempore sp. nov. is proposed to accommodate these strains. The type strain is 11-1170T (=CBS 14366T=CCY 094-001-001T=NCAIM-Y02177T) isolated in Cagayan de Oro, The Philippines. Mycobank: MB 817222.

  6. New Clinically Relevant Findings about Violence by People with Schizophrenia. (United States)

    Hodgins, Sheilagh; Klein, Sanja


    To review findings with clinical relevance that add to knowledge about antisocial and aggressive behaviour among persons with schizophrenia. Nonsystematic literature review. Recent evidence shows that individuals who develop schizophrenia present cognitive deficits, psychotic-like experiences, and internalizing and externalizing problems from childhood onwards. Many of their relatives present not only schizophrenia-related disorders but also antisocial behaviour. While the increased risk of aggressive behaviour among persons with schizophrenia has been robustly established, recent findings show that by first contact with clinical services for psychosis, most people with schizophrenia who will engage in aggressive behaviour may be identified. At first episode, 2 distinct types are distinguishable: those who present a history of antisocial and aggressive behaviour since childhood and those who began engaging in aggressive behaviour as illness onsets. Antipsychotic medications and other treatments shown to be effective for schizophrenia are needed by both types of patients. Additionally, those with a history of antisocial and aggressive behaviour since childhood require cognitive-behavioural programs aimed at reducing these behaviours and promoting prosocial behaviour. Reducing physical victimisation and cannabis use will likely reduce aggressive behaviour. Evidence suggests that threats to hurt others often precede assaults. At first contact with services, patients with schizophrenia who have engaged in aggressive behaviour should be identified and treated for schizophrenia and for aggression. Research is needed to identify interactions between genotypes and environmental factors, from conception onwards, that promote and that protect against the development of aggressive behaviour among persons with schizophrenia.

  7. Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance

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    Audrey E. McCalley


    Full Text Available Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol’s mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol’s actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  8. Rapid identification of bacteria and candida using pna-fish from blood and peritoneal fluid cultures: a retrospective clinical study

    Directory of Open Access Journals (Sweden)

    Harris Dana M


    Full Text Available Abstract Background Peptide nucleic acid fluorescent in situ hybridization (PNA-FISH is a rapid and established method for identification of Candida sp., Gram positive, and Gram negative bacteria from positive blood cultures. This study reports clinical experience in the evaluation of 103 positive blood cultures and 17 positive peritoneal fluid cultures from 120 patients using PNA-FISH. Our study provides evidence as to potential pharmaceutical cost savings based on rapid pathogen identification, in addition to the novel application of PNA-FISH to peritoneal fluid specimens. Methods Identification accuracy and elapsed time to identification of Gram positives, Gram negatives, and Candida sp., isolated from blood and peritoneal fluid cultures were assessed using PNA-FISH (AdvanDx, as compared to standard culture methods. Patient charts were reviewed to extrapolate potential pharmaceutical cost savings due to adjustment of antimicrobial or antifungal therapy, based on identification by PNA-FISH. Results In blood cultures, time to identification by standard culture methods for bacteria and Candida sp., averaged 83.6 hours (95% CI 56.7 to 110.5. Identification by PNA-FISH averaged 11.2 hours (95% CI 4.8 to 17.6. Overall PNA-FISH identification accuracy was 98.8% (83/84, 95% CI 93.5% to 99.9% as compared to culture. In peritoneal fluid, identification of bacteria by culture averaged 87.4 hours (95% CI −92.4 to 267.1. Identification by PNA-FISH averaged 16.4 hours (95% CI −57.3 to 90.0. Overall PNA-FISH identification accuracy was 100% (13/13, 95% CI 75.3% to 100%. For Candida sp., pharmaceutical cost savings based on PNA-FISH identification could be $377.74/day. For coagulase-negative staphylococcus (CoNS, discontinuation of vancomycin could result in savings of $20.00/day. Conclusions In this retrospective study, excellent accuracy of PNA-FISH in blood and peritoneal fluids with reduced time to identification was observed, as compared to

  9. In vitro photodynamic inactivation effects of cationic benzylidene cyclopentanone photosensitizers on clinical fluconazole-resistant Candida albicans planktonic cells and biofilms (United States)

    Zhou, Shaona; Fang, Yanyan; Ye, Zulin; Wang, Ying; Zhao, Yuxia; Gu, Ying


    Background: An increasing prevalence of Candida infections has emerged with the wide use of immune-suppressants and antibiotics. Photodynamic inactivation (PDI) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. This study evaluated the efficacy of photodynamic therapy using two new Cationic benzylidene cyclopentanone photosensitizers(P1 and P2) against strains of clinical fluconazole-resistant Candida albicans. Methods: Suspensions and biofilms of Candida species were incubated with P1 and P2 concentrations (0.25 50 μM) for 30 min followed by 532nm laser irradiation. For planktonic suspensions, viability of cells was assayed by CFU counting. For biofilms, the metabolic activity was evaluated by XTT. Results: In PDI of a planktonic culture of clinical fluconazole-resistant Candida albicans, P2 showed the higher efficacy. After incubation with 25 μM of P2 for 30 min and irradiation with 532nm laser (36 J cm-2), the viability of C. albicans planktonic cells decreased by 3.84 log10. For biofilm cells, a higher light dose of 75 mW cm-2 was necessary to achieve 97.71% metabolic activity reduction. Conclusions: The results of this investigation demonstrated that benzylidene cyclopentanone photosensitizer, P2, is an efficient photosensitizer to kill C. albicans. Moreover, single-species biofilms were less susceptible to PDT than their planktonic counterparts.

  10. Selected Essential Oils as Antifungal Agents Against Antibiotic-Resistant Candida spp.: In Vitro Study on Clinical and Food-Borne Isolates. (United States)

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Maroszyńska, Marta


    Candida spp. cause significant health problems, inducing various types of superficial and deep-seated mycoses in humans. As a result of the increasing antibiotic resistance among pathogenic yeasts, the interest in alternative agents of antifungal activity is growing. This study evaluated the antimicrobial activity of selected essential oils (EOs) against Candida clinical and food-borne strains, including antibiotic-resistant isolates, in relation to yeast cell surface hydrophobicity (CSH). Candida strains showed different range of susceptibility to tea tree, thyme, peppermint, and clove oils, and peppermint oil demonstrated the lowest anticandidal activity with minimal inhibitory concentrations (MICs) of 0.03-8.0% v/v. MIC values for thyme and clove oils ranged from 0.03% to 0.25% v/v, and for tea tree oil-from 0.12% to 2.0% v/v. The exception was Candida tropicalis food-borne strain, the growth of which was inhibited after application of EOs at concentration of 8% v/v. Due to diverse yeast susceptibility to EOs, isolates were divided into five clusters in a principal component analysis model, each containing both clinical and food-borne strains. Hydrophobic properties of yeast were also diversified, and 37% of clinical and 50% of food-borne strains exhibited high hydrophobicity. The study indicates high homology of clinical and food-borne Candida isolates in relation to their susceptibility to anticandidal agents and hydrophobic properties. The susceptibility of yeasts to EOs could be partially related to their CSH. High antifungal activity of examined EOs, also against antibiotic-resistant isolates, indicates their usefulness as agents preventing the development of Candida strains of different origin.

  11. The Use of Chitosan to Enhance Photodynamic Inactivation against Candida albicans and Its Drug-Resistant Clinical Isolates

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    Tsuimin Tsai


    Full Text Available Drug-resistant Candida infection is a major health concern among immunocompromised patients. Antimicrobial photodynamic inactivation (PDI was introduced as an alternative treatment for local infections. Although Candida (C. has demonstrated susceptibility to PDI, high doses of photosensitizer (PS and light energy are required, which may be harmful to eukaryotic human cells. This study explores the capacity of chitosan, a polycationic biopolymer, to increase the efficacy of PDI against C. albicans, as well as fluconazole-resistant clinical isolates in planktonic or biofilm states. Chitosan was shown to effectively augment the effect of PDI mediated by toluidine blue O (TBO against C. albicans that were incubated with chitosan for 30 min following PDI. Chitosan at concentrations as low as 0.25% eradicated C. albicans; however, without PDI treatment, chitosan alone did not demonstrate significant antimicrobial activity within the 30 min of incubation. These results suggest that chitosan only augmented the fungicidal effect after the cells had been damaged by PDI. Increasing the dosage of chitosan or prolonging the incubation time allowed a reduction in the PDI condition required to completely eradicate C. albicans. These results clearly indicate that combining chitosan with PDI is a promising antimicrobial approach to treat infectious diseases.

  12. Candida albicans or Candida dubliniensis? (United States)

    Ells, Ruan; Kock, Johan L F; Pohl, Carolina H


    Candida albicans is increasing as an opportunistic pathogen causing candidemia and candidiasis worldwide. In addition, other non-albicans Candida species are now also associated with pertinent infections. These include the closely related C. dubliniensis, which shares many phenotypic similarities with C. albicans. These similarities pose problems in the identification of isolates and have previously led to misidentification of these species. As a result, several identification techniques based on phenotypic and genotypic characteristics have been developed to differentiate between these Candida species. This review will focus on the similarities and differences between these two Candida species highlighting different identification methods and their advantages and disadvantages. © 2009 Blackwell Verlag GmbH.

  13. The clinical relevance of orthostatic hypotension in elderly patients. (United States)

    Hartog, Laura; Kleefstra, Nanne; Luigies, Rene; de Rooij, Sophia; Bilo, Henk; van Hateren, Kornelis


    Orthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints. We aimed to explore the relation between different definitions of OH, including relative decrease of blood pressure, and orthostatic complaints and falling. A cross-sectional study was performed with 1415 participants aged ≥65 years visiting a mobile fall-prevention team. The CAREFALL Triage Instrument and data on blood pressure, orthostatic complaints and previous fall incidents were collected. Multivariate binary logistic regression analyses were performed to assess the association of different definitions of OH and orthostatic complaints or falling. Ten different definitions of OH based on different relative declines of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were defined. The 2011 consensus definition of OH was not related to orthostatic complaints (Odds Ratio (OR) 1.07 (95 % Confidence Interval (CI) 0.68-1.69)) or previous fall incidents (OR 1.08 (95%CI 0.83-1.41)). A ≥ 25 % SBP decrease was significantly related to orthostatic complaints (OR 2.81 (95%CI 1.31-6.05)) and a ≥ 25 % DBP decrease was related to previous fall incidents (OR 2.56 (95%CI 1.08-6.09)). With the exception of a decrease of ≥25 % SBP or DBP, the clinical relevance of incidental OH blood pressure measurements seems very limited with respect to orthostatic complaints or fall incidents in elderly patients. Using relative decreases may be more appropriate in clinical practice. Geriatr Gerontol Int 2016; ••: ••-••. © 2017 Japan Geriatrics Society.

  14. [Clinical relevance of tooth brushing in relation to dental caries]. (United States)

    Pita-Fernández, Salvador; Pombo-Sánchez, Antonio; Suárez-Quintanilla, Juan; Novio-Mallón, Silvia; Rivas-Mundiña, Berta; Pértega-Díaz, Sonia


    To determine the impact and clinical relevance of tooth brushing on oral health. Prevalence study. Fontiñas Health Centre. (Santiago de Compostela, Spain). Prevalence study (n=281 children aged 5-14 years. Odontological examination according to WHO methodology, to determine the frequency of tooth brushing, frequency of sweet consumption and their impact on the prevalence of caries. Logistic regression and estimation of the relative prevalence difference (RPD) and the Number Needed to Treat in order to prevent one additional bad outcome (NNT). The children who never brush their teeth have a 40% (95% CI: 24.3%-57.8%) of early caries, while those who brush their teeth several times a day have 15.3% (95% CI: 9.4%-23.7%). An association between not brushing the teeth and caries in primary teeth (OR=2.3; 95% CI:1.05-5.3) was observed after adjusting for age, sweet consumption and visits to the dentist. The same occurred with final teeth (OR=3.9; 95% CI:1.4-10.3). The RPD was 62%(95% CI: 30%-79%), meaning that prevalence of caries is 62% lower in children who brush their teeth several times a day as compared to those who never brush their teeth. The NNT is 4 (95% CI: 2.4-14), so for every 4 children who brush their teeth several times a day, there is one less case of caries, compared to those who never brush their teeth. There is a dose-response relationship between prevalence of caries and brushing frequency. The same effect was observed with definitive caries: RPD=55% (95% CI:16%-76%), NNT=5 (95% CI:2.8-53.3). Tooth brushing is related to oral health, with a major clinical impact. The positive effect of tooth brushing was superior to that of a correct diet. 2009 Elsevier España, S.L. All rights reserved.

  15. Clinical Relevance of Autoantibodies in Patients with Autoimmune Bullous Dermatosis

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    Lilla Mihályi


    Full Text Available The authors present their experience related to the diagnosis, treatment, and followup of 431 patients with bullous pemphigoid, 14 patients with juvenile bullous pemphigoid, and 273 patients with pemphigus. The detection of autoantibodies plays an outstanding role in the diagnosis and differential diagnosis. Paraneoplastic pemphigoid is suggested to be a distinct entity from the group of bullous pemphigoid in view of the linear C3 deposits along the basement membrane of the perilesional skin and the “ladder” configuration of autoantibodies demonstrated by western blot analysis. It is proposed that IgA pemphigoid should be differentiated from the linear IgA dermatoses. Immunosuppressive therapy is recommended in which the maintenance dose of corticosteroid is administered every second day, thereby reducing the side effects of the corticosteroids. Following the detection of IgA antibodies (IgA pemphigoid, linear IgA bullous dermatosis, and IgA pemphigus, diamino diphenyl sulfone (dapsone therapy is preferred alone or in combination. The clinical relevance of autoantibodies in patients with autoimmune bullous dermatosis is stressed.

  16. Clinical Relevance of HLA Gene Variants in HBV Infection

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    Li Wang


    Full Text Available Host gene variants may influence the natural history of hepatitis B virus (HBV infection. The human leukocyte antigen (HLA system, the major histocompatibility complex (MHC in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs have shown that single nucleotide polymorphisms (SNPs near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC in chronic hepatitis B (CHB. These variations also influence the efficacy of interferon (IFN and nucleot(side analogue (NA treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

  17. Epileptic neuronal networks: methods of identification and clinical relevance. (United States)

    Stefan, Hermann; Lopes da Silva, Fernando H


    The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and "generalized" epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called "generalized epilepsies," such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed.

  18. Effectiveness of a Clinically Relevant Educational Program for Improving Medical Communication and Clinical Skills of International Medical Graduates

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    David Watt


    Conclusions:  IMGs who participated in a clinically relevant educational program improved their English language proficiency, clinical skills and professionalism for medical practice in a host country.

  19. Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. (United States)

    Pfaller, M A; Andes, D; Diekema, D J; Espinel-Ingroff, A; Sheehan, D


    Both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have MIC clinical breakpoints (CBPs) for fluconazole (FLU) and Candida. EUCAST CBPs are species-specific, and apply only to C. albicans, C. tropicalis and C. parapsilosis, while CLSI CBPs apply to all species. We reassessed the CLSI CBPs for FLU and Candida in light of recent data. We examined (1) molecular mechanisms of resistance and cross-resistance profiles, (2) wild-type (WT) MICs and epidemiological cutoff values (ECVs) for FLU and major Candida species by both CLSI and EUCAST methods, (3) determination of essential (EA) and categorical agreement (CA) between CLSI and EUCAST methods, (4) correlation of MICs with outcomes from previously published data using CLSI and EUCAST methods, and (5) pharmacokinetic and pharmacodynamic considerations. We applied these findings to propose new species-specific CLSI CBPs for FLU and Candida. WT distributions from large collections of Candida revealed similar ECVs by both CLSI and EUCAST methods (0.5-1 mcg/ml for C. albicans, 2 mcg/ml for C. parapsilosis and C. tropicalis, 32 mcg/ml for C. glabrata, and 64-128 for C. krusei). Comparison of CLSI and EUCAST MICs reveal EA and CA of 95% and 96%, respectively. Datasets correlating CLSI and EUCAST FLU MICs with outcomes revealed decreased response rates when MICs were > 4 mcg/ml for C. albicans, C. tropicalis and C. parapsilosis, and > 16 mcg/ml for C. glabrata. Adjusted CLSI CBPs for FLU and C. albicans, C. parapsilosis, C. tropicalis (S, ≤ 2 mcg/ml; SDD, 4 mcg/ml; R, ≥ 8 mcg/ml), and C. glabrata (SDD, ≤ 32 mcg/ml; R, ≥ 64 mcg/ml) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. In vitro susceptibility of Candida albicans clinical isolates to eight antifungal agents in Ouagadougou (Burkina Faso). (United States)

    Zida, A; Yacouba, A; Bamba, S; Sangare, I; Sawadogo, M; Guiguemde, T; Kone, S; Traore, L K; Ouedraogo-Traore, R; Guiguemde, R T


    In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant. Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates. In vitro C. albicans antifungal susceptibility test in this study showed relatively high

  1. Cardiac Remote Conditioning and Clinical Relevance: All Together Now!

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    Kristin Luther


    mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective “conditioning” phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-кB, Stat3/5, protein kinase C, bradykinin, and the mitoKATP channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

  2. Vulvovaginal candidosis caused by Candida non-albicans, proportion and clinical characteristics in the Dr. Cipto Mangunkusumo National General Hospital, Jakarta

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    Midi Haryani


    Full Text Available The prevalence of vulvovaginal candidosis (VVC caused by C. non-albicans tends to increase, recently. The aim of this study was to obtain data about proportion and clinical characteristic of C. non-albicans VVC at dr. Cipto Mangunkusumo General Hospital, Jakarta. This is a cross-sectional study on all female patients with symptoms of VVC visiting Obstetri-gynaecology and Dermatovenereology outpatient clinics at dr. Cipto Mangunkusumo General Hospital, Jakarta. All subjects had positive Gram stain, showed Candida spp. on culture with CHROMagar Candida, and had no other specific genital infections. Sixty nine subjects aged 26–44 years old (averaged 29 years old were included in this study. Candida non-albicans was found in 30.4% subject, and consisted of: C. glabrata (61.9%, C. tropicalis (28.6% and C. parapsilosis (9.5%. We found that C. non-albicans VVC infections are more common in women above 45 years old, using non-hormonal contraceptives, whose sexual partner has erythema and pruritus in glands penis, and having the disease for more than 1 year. No differences in clinical symptoms were noted between C. albicans and C. non-albicans infection. We concluded from this study that the proportion of C. non-albicans infections at dr. Cipto Mangunkusumo General Hospital, Jakarta, with C. glabrata represents the most prevalent species. No characteristic clinical symptoms were found from the subjects with C. non-albicans VVC when compared with those infected by C. albicans. (Med J Indones 2003; 12: 142-7 Keywords: vulvovaginal candidosis, Candida non-albicans, CHROMagar Candida

  3. In vitro differential activity of phospholipases and acid proteinases of clinical isolates of Candida Atividade diferencial in vitro de fosfolipases e proteinases ácidas de isolados clínicos de Candida

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    Aurean D'Eça Júnior


    Full Text Available INTRODUCTION: Candida yeasts are commensals; however, if the balance of normal flora is disrupted or the immune defenses are compromised, Candida species can cause disease manifestations. Several attributes contribute to the virulence and pathogenicity of Candida, including the production of extracellular hydrolytic enzymes, particularly phospholipase and proteinase. This study aimed to investigate the in vitro activity of phospholipases and acid proteinases in clinical isolates of Candida spp. METHODS: Eighty-two isolates from hospitalized patients collected from various sites of origin were analyzed. Phospholipase production was performed in egg yolk medium and the production of proteinase was verified in a medium containing bovine serum albumin. The study was performed in triplicate. RESULTS: Fifty-six (68.3% of isolates tested were phospholipase positive and 16 (44.4% were positive for proteinase activity. C. tropicalis was the species with the highest number of positive isolates for phospholipase (91.7%. Statistically significant differences were observed in relation to production of phospholipases among species (pINTRODUÇÃO: Candida são leveduras comensais, porém, se o equilíbrio da flora normal for interrompido ou as defesas imunitárias estiverem comprometidas, espécies de Candida podem causar manifestações de doença. Vários atributos contribuem na virulência e patogenicidade de Candida, inclusive a produção de enzimas extracelulares hidrolíticas, especialmente fosfolipases e proteinases. O objetivo deste estudo foi verificar a atividade in vitro de fosfolipases e proteinases ácidas em isolados clínicos de Candida spp. MÉTODOS: Oitenta e dois isolados provenientes de pacientes hospitalizados coletados a partir de sítios de origem diversos foram analisados. A produção de fosfolipase foi verificada em meio egg yolk e a de proteinase em meio contendo soro albumina bovina. O estudo foi feito em triplicata. RESULTADOS

  4. The identification of Candida species isolated from clinical specimens of immunocompromised patients with PCR and determination of antifungal resistance genes with RFLP and sequencing analysis

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    Yıldız Yeğenoğlu


    Full Text Available Objectives: The aim of this study is to investigate PCRtechnique and antifungal resistance genes with RFLP andsequencing analysis in Candida species isolated fromclinical specimens of immune-compromised patients.Materials and methods: Clinical samples (96 bronchoalveolarlavages, 56 biopsy-abscess, 8 blood specimens,15 peritoneal fluid specimens, 15 pleural fluid, 5 cerebrospinalfluid and 5 pericard fluid specimens from 200 immunosuppressedpatients were studied by conventionaland molecular methods. Antifungal susceptibility testingwas performed by the E-test method. Firstly, fungal DNAwas isolated from specimens, and then the resultantproducts are defined with multiplex PCR. Antifungal resistanceand resistance genes were established by E-testand RFLP analysis.Results: Thirty of 200 samples (15% were culture positive[20 Candida albicans (67%, five Candida parapsilosis(17%, five Candida tropicalis (17%], and 170 ofsamples were found culture negative (85%. PCR with theuniversal primers detected fungal DNA in all 30 culturepositive samples. One strain was determined as resistant;2 strains were dose dependent susceptible and 27 strainswere sensitive to fluconazole by E-test. The resistancegene (ERG11 was detected by BamHI and SalI enzymesrevealed fluconazole resistance in one of C.albicansstrains. The identification was successful in Candida dubliniensis(950 bp and Candida krusei (360 bp with multiplexPCR. D132E and E216D mutations were detected insequencing of ERG 11 gene of this isolate and comparedwith reference gene in GenBank by clustal analysis.Conclusion: The molecular test methods supplies correcttherapy rather early in immunosuppressive patientstherefore it is important for the survival.

  5. Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example. (United States)

    Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J


    Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Gene editing in clinical isolates of Candida parapsilosis using CRISPR/Cas9. (United States)

    Lombardi, Lisa; Turner, Siobhán A; Zhao, Fang; Butler, Geraldine


    Candida parapsilosis is one of the most common causes of candidiasis, particularly in the very young and the very old. Studies of gene function are limited by the lack of a sexual cycle, the diploid genome, and a paucity of molecular tools. We describe here the development of a plasmid-based CRISPR-Cas9 system for gene editing in C. parapsilosis. A major advantage of the system is that it can be used in any genetic background, which we showed by editing genes in 20 different isolates. Gene editing is carried out in a single transformation step. The CAS9 gene is expressed only when the plasmid is present, and it can be removed easily from transformed strains. There is theoretically no limit to the number of genes that can be edited in any strain. Gene editing is increased by homology-directed repair in the presence of a repair template. Editing by non-homologous end joining (NHEJ) also occurs in some genetic backgrounds. Finally, we used the system to introduce unique tags at edited sites.

  7. Clinical management of Candida albicans keratomycosis in a bottlenose dolphin (Tursiops truncatus). (United States)

    Simeone, Claire A; Traversi, John P; Meegan, Jenny M; LeBert, Carolina; Colitz, Carmen M H; Jensen, Eric D


    Corneal ulceration secondary to trauma commonly affects marine mammals, often with opportunistic secondary bacterial or fungal infections. This report characterizes the combined use of auriculopalpebral and ophthalmic nerve blocks, adipose-derived stem cells, and subconjunctival injections for successful treatment of corneal trauma and infection in dolphins. An 11-year-old, female bottlenose dolphin (Tursiops truncatus) presented with bilateral diffuse corneal opacities, which progressed to keratomycosis caused by Candida albicans. Aggressive medical management was employed, including the use of subconjunctival injections of adipose-derived stem cells, plasma, topical and oral antifungals and antibiotics, and anti-inflammatory and pain medications. Anesthetic block of the auriculopalpebral and ophthalmic nerves was employed to evaluate the corneas. Subconjunctival injections were employed over 52 days, followed by topical drops for 5 months. At last evaluation, there was no evidence of blepharospasm bilaterally. Only a faint superficial gray corneal opacity remained OS. A temporal paraxial corneal opacity was present OD, with receding inactive vascularization and a small amount of melanosis temporally. © 2017 American College of Veterinary Ophthalmologists.

  8. Assessment of antifungal activity of herbal and conventional toothpastes against clinical isolates of Candida albicans (United States)

    Adwan, Ghaleb; Salameh, Yousef; Adwan, Kamel; Barakat, Ali


    Objective To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans (C. albicans) isolates. Methods The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method. Statistical analysis was performed using a statistical package, SPSS windows version 15, by applying mean values using one-way ANOVA with post-hoc least square differences (LSD) method. A P value of less than 0.05 was considered significant. Results All toothpastes studied in our experiments were effective in inhibiting the growth of all C. albicans isolates. The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient. Antifungal activity of Parodontax toothpaste showed a significant difference (Ptoothpastes containing sodium fluoride or herbal products. Conclusions In the present study, it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C. albicans, while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C. albicans. Some herbal toothpaste formulations studied in our experiments, appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products. Our results may provide invaluable information for dental professionals. PMID:23569933

  9. [Clinical studies in oncology. Relevance, design, ethical considerations]. (United States)

    Wörmann, B; Wulf, G; Hiddemann, W


    Clinical research in oncology includes the evaluation of diagnostic, prognostic and therapeutic parameters in order to establish standards for the different tumor entities. Prerequisite is the retrospective and prospective analysis of large patient groups with established statistical methods. New potentially better strategies have to be compared in randomised studies with the respective "gold standard". The central role of clinical studies for evaluation and optimisation of therapy can be considered as moral obligation to included the maximal possible number of patients in clinical studies. However, only a small number of tumor patients in Germany is treated in controlled clinical studies. Reasons are lack of organisational structures, but also ethical considerations. In this article several models for clinical studies are discussed with respect to their statistical significance, indication, and potential ethical objections. Aim of the discussion is to increase the acceptance of the necessity of clinical studies for evaluation and optimisation of therapeutic options in oncology.

  10. The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates. (United States)

    Holmes, Ann R; Keniya, Mikhail V; Ivnitski-Steele, Irena; Monk, Brian C; Lamping, Erwin; Sklar, Larry A; Cannon, Richard D


    Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant Saccharomyces cerevisiae strains hyperexpressing individual transporters from the opportunistic fungal pathogen Candida albicans. The recombinant strains possess greater resistance to azoles and other pump substrates than the parental host strain. A flow cytometry-based HTS, which measured increased intracellular retention of the fluorescent pump substrate rhodamine 6G (R6G) within yeast cells, was used to screen the Prestwick Chemical Library (PCL) of 1,200 marketed drugs. Nine compounds were identified as hits, and the monoamine oxidase A inhibitor (MAOI) clorgyline was identified as an inhibitor of two C. albicans ABC efflux pumps, CaCdr1p and CaCdr2p. Secondary in vitro assays confirmed inhibition of pump-mediated efflux by clorgyline. Clorgyline also reversed the FLC resistance of S. cerevisiae strains expressing other individual fungal ABC transporters (Candida glabrata Cdr1p or Candida krusei Abc1p) or the C. albicans MFS transporter Mdr1p. Recombinant strains were also chemosensitized by clorgyline to other azoles (itraconazole and miconazole). Importantly, clorgyline showed synergy with FLC against FLC-resistant C. albicans clinical isolates and a C. glabrata strain and inhibited R6G efflux from a FLC-resistant C. albicans clinical isolate. Clorgyline is a novel broad-spectrum inhibitor of two classes of fungal efflux pumps that acts synergistically with azoles against azole-resistant C. albicans and C. glabrata strains.

  11. A comparison of the clinical relevance of thallium201 and ...

    African Journals Online (AJOL)

    Thallium-201 is at present the radiotracer of choice for the clinical evaluation of myocardial blood flow. Although different technetium-99m-isonitrile agents have been synthesised recently, only 99mTc-melhoxyisobutyl-isonitrile (99mTc_MIBI) has proved to hold promise for clinical implementation. The myocardial distribution ...

  12. Evidence-Based Clinical Significance in Health Care: Toward an Inferential Analysis of Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Mahsa Dousti


    Full Text Available Evidence-based dental practice requires the developmment and evaluation of protocols that en-sure translational effectiveness: that is, the efficient incorporation of the best available efficacy and effec-tiveness findings in specific clinical dentistry settings and environments. Evidence-based dentistry predi-cates the synthesis of research for obtaining the best available evidence in a validated, stringent, systematic and unbiased fashion. Research synthesis is now established as a science in its own right, precisely because it adheres to the scientific process that is driven by a research question and a hypothesis, follows through clearly defined methodology and design, yielding quantifiable data that are analyzed statistically, and from which stringent statistical inferences are drawn. The conclusions from the protocol of research synthesis define the best available evidence, which is used in the process of evidence-based revision of clinical practice guidelines. One important hurdle of the process of applying research synthesis in evidence-based dentistry lies in the fact that the statistical inferences produced by research must be translated into clinical relevance. Here, we present a model to circumvent this limitation by means of text analysis/mining protocols, which could lead the path toward a novel, valid and reliable ap-proach for the inferential analysis of clinical relevance.

  13. Mechanistic Insights Underlying Tolerance to Acetic Acid Stress in Vaginal Candida glabrata Clinical Isolates. (United States)

    Cunha, Diana V; Salazar, Sara B; Lopes, Maria M; Mira, Nuno P


    During colonization of the vaginal tract Candida glabrata cells are challenged with the presence of acetic acid at a low pH, specially when dysbiosis occurs. To avoid exclusion from this niche C. glabrata cells are expected to evolve efficient adaptive responses to cope with this stress; however, these responses remain largely uncharacterized, especially in vaginal strains. In this work a cohort of 18 vaginal strains and 2 laboratory strains (CBS138 and KUE100) were phenotyped for their tolerance against inhibitory concentrations of acetic acid at pH 4. Despite some heterogeneity has been observed among the vaginal strains tested, in general these strains were considerably more tolerant to acetic acid than the laboratory strains. To tackle the mechanistic insights behind this differential level of tolerance observed, a set of vaginal strains differently tolerant to acetic acid (VG281∼VG49 acetic acid the more tolerant vaginal strains exhibited a higher activity of the plasma membrane proton pump CgPma1 and a reduced internal accumulation of the acid, these being two essential features to maximize tolerance. Based on the higher level of resistance exhibited by the vaginal strains against the action of a β-1,3-glucanase, it is hypothesized that the reduced internal accumulation of acetic acid inside these strains may originate from them having a different cell wall structure resulting in a reduced porosity to undissociated acetic acid molecules. Both the vaginal and the two laboratory strains were found to consume acetic acid in the presence of glucose indicating that metabolization of the acid is used by C. glabrata species as a detoxification mechanism. The results gathered in this study advance the current knowledge on the mechanisms underlying the increased competitiveness of C. glabrata in the vaginal tract, a knowledge that can be used to guide more suitable strategies to treat infections caused by this pathogenic yeast.

  14. Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands.

    NARCIS (Netherlands)

    Ingen, J. van; Bendien, S.A.; Lange, W.C.M. de; Hoefsloot, W.; Dekhuijzen, P.N.R.; Boeree, M.J.; Soolingen, D. van


    BACKGROUND: The frequency of clinical isolation of non-tuberculous mycobacteria (NTM) in the Netherlands is increasing, but its clinical relevance is often uncertain. OBJECTIVE: To assess the frequency and clinical relevance of isolation of NTM in four associated hospitals in a single region in the

  15. In vitro fluconazole susceptibility of 1,903 clinical isolates of Candida albicans and the identification of ERG11 mutations. (United States)

    Ying, Ying; Zhao, Yingjie; Hu, Xuefei; Cai, Zhenyu; Liu, Xin; Jin, Guilin; Zhang, Jieyu; Zhang, Jingyi; Liu, Jinhui; Huang, Xiaotian


    Abstract Fluconazole resistance of Candida albicans has been reported to be the result of one or more specific point mutations in ERG11 gene. In this study, we amplified and sequenced the entire ERG11 coding sequence of 72 isolates of C. albicans to search for possible mutations. Twenty-seven silent mutations and 14 missense mutations were identified. While the mutations K342R and V437I were found as single-amino-acid changes in Erg11p, other mutations were detected simultaneously in individual isolates. Several different clinical isolates had the same pattern of multiple amino acid alternations: (1) A114S with Y257H was identified in 11 resistant and 3 susceptible dose-dependent isolates without any other silent mutation and may be associated with resistance; (2) Y132H combined with G450E was identified in two fluconazole-resistant isolates and is known to contribute to resistance; and (3) the coexistence of D116E, K128T, Y132H, and G465S was first described in five reduced-susceptibility isolates, but the correlation of this pattern with resistance is still uncertain. These data indicate that multiple amino acid substitutions in Erg11p were found frequently in clinical isolates and may be associated with fluconazole resistance.

  16. Decaying relevance of clinical data towards future decisions in data-driven inpatient clinical order sets. (United States)

    Chen, Jonathan H; Alagappan, Muthuraman; Goldstein, Mary K; Asch, Steven M; Altman, Russ B


    Determine how varying longitudinal historical training data can impact prediction of future clinical decisions. Estimate the "decay rate" of clinical data source relevance. We trained a clinical order recommender system, analogous to Netflix or Amazon's "Customers who bought A also bought B..." product recommenders, based on a tertiary academic hospital's structured electronic health record data. We used this system to predict future (2013) admission orders based on different subsets of historical training data (2009 through 2012), relative to existing human-authored order sets. Predicting future (2013) inpatient orders is more accurate with models trained on just one month of recent (2012) data than with 12 months of older (2009) data (ROC AUC 0.91 vs. 0.88, precision 27% vs. 22%, recall 52% vs. 43%, all P<10 -10 ). Algorithmically learned models from even the older (2009) data was still more effective than existing human-authored order sets (ROC AUC 0.81, precision 16% recall 35%). Training with more longitudinal data (2009-2012) was no better than using only the most recent (2012) data, unless applying a decaying weighting scheme with a "half-life" of data relevance about 4 months. Clinical practice patterns (automatically) learned from electronic health record data can vary substantially across years. Gold standards for clinical decision support are elusive moving targets, reinforcing the need for automated methods that can adapt to evolving information. Prioritizing small amounts of recent data is more effective than using larger amounts of older data towards future clinical predictions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Clinical performance of the (1,3)-β-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections. (United States)

    Del Bono, Valerio; Delfino, Emanuele; Furfaro, Elisa; Mikulska, Malgorzata; Nicco, Elena; Bruzzi, Paolo; Mularoni, Alessandra; Bassetti, Matteo; Viscoli, Claudio


    Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-D-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first Candida-positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.

  18. Adaptations in the wall proteome of the clinical fungus Candida albicans in response to infection-related environmental conditions

    NARCIS (Netherlands)

    Sosińska, G.J.


    De pathogene schimmel Candida albicans past zijn celwandproteoom voortdurend aan aan uiteenlopende omgevingsomstandigheden die het aantreft in de gastheer. Dat levert sterke aanwijzingen op voor nieuwe aangrijpingspunten voor antischimmelmiddelen en voor nieuwe vaccinkandidaten. Dat blijkt uit

  19. Clinical relevance of sonographically estimated amniotic fluid volume: polyhydramnios. (United States)

    Sandlin, Adam T; Chauhan, Suneet P; Magann, Everett F


    Polyhydramnios is an excessive amount of amniotic fluid within the amniotic cavity. The etiology of polyhydramnios may be idiopathic, the consequence of fetal structural anomalies, or the consequence of various fetal and maternal conditions. The clinical importance of polyhydramnios is found in its association with adverse pregnancy outcomes and the risk of perinatal mortality. The antenatal management of polyhydramnios can be challenging as there are no formalized guidelines on the topic. The purpose of this review is to provide a literature-based overview on the subject of polyhydramnios in singleton pregnancies, demonstrate its clinical implications, and describe a practical approach to its management.

  20. Pharmacogenetics in Cardiovascular Disease is there clinical relevance?

    NARCIS (Netherlands)

    Maitland-Van Der Zee, A.


    • Objectives: To give an up-to-date overview of the research in pharmacogenetics of cardiovascular disease, and the clinical implications of this research. • Methods: In this lecture I will focus on these groups cardiovascular drugs where many pharmacogenetics studies have been performed (including

  1. The placebo response: neurobiological and clinical issues of neurological relevance. (United States)

    Pollo, Antonella; Benedetti, Fabrizio


    The recent upsurge in placebo research has demonstrated the sound neurobiological substrate of a phenomenon once believed to be only patient mystification, or at best a variable to control in clinical trials, bringing about a new awareness of its potential exploitation to the patient's benefit and framing it as a positive context effect, with the power to influence the therapy outcome. Placebo effects have been described both in the experimental setting and in different clinical conditions, many of which are of neurological interest. Multiple mechanisms have been described, namely conditioning and cognitive factors like expectation, desire, and reward. A body of evidence from neurochemical, pharmacological, and neuroimaging studies points to the involvement of neural pathways specific to single conditions, such as the activation of the endogenous antinociceptive system during placebo analgesia or the release of dopamine in the striatum of parkinsonian patients experiencing placebo reduction of motor impairment. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient, in order to maximize the placebo component present in any treatment.

  2. Developing independent investigators for clinical research relevant for Africa

    LENUS (Irish Health Repository)

    Manabe, Yukari C


    Abstract Sustainable research capacity building requires training individuals at multiple levels within a supportive institutional infrastructure to develop a critical mass of independent researchers. At many African medical institutions, a PhD is important for academic promotion and is, therefore, an important focal area for capacity building programs. We examine the training at the Infectious Diseases Institute (IDI) as a model for in-country training based on systems capacity building and attention to the academic environment. PhD training in Africa should provide a strong research foundation for individuals to perform independent, original research and to mentor others. Training the next generation of researchers within excellent indigenous academic centers of excellence with strong institutional infrastructure will empower trainees to ask regionally relevant research questions that will benefit Africans.

  3. Clinical relevance of drug-drug interactions : a structured assessment procedure.

    NARCIS (Netherlands)

    Roon, E.N. van; Flikweert, S.; Comte, M. le; Langendijk, P.N.; Kwee-Zuiderwijk, W.J.; Smits, P.; Brouwers, J.R.B.J.


    INTRODUCTION: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for the

  4. Clinical relevance of drug-drug interactions - A structured assessment procedure

    NARCIS (Netherlands)

    van Roon, EN; Flikweert, S; le Comte, M; Langendijk, PNJ; Kwee-Zuiderwijk, WJM; Smits, P; Brouwers, JRBJ


    Introduction: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS C, reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for

  5. Clinical relevance of rehospitalizations for unstable angina and unplanned revascularization following acute myocardial infarction

    NARCIS (Netherlands)

    Shore, Supriya; Smolderen, K.G.E.; Spertus, John A.; Kennedy, Kevin F.; Jones, Philip G.; Zhao, Zhenxiang; Wang, Tracy Y.; Arnold, Suzanne V.


    Background Rehospitalizations following acute myocardial infarction for unplanned coronary revascularization and unstable angina (UA) are often included as parts of composite end points in clinical trials. Although clearly costly, the clinical relevance of these individual components has not been

  6. Evaluation of the in vitro activity of isavuconazole and comparator voriconazole against 2635 contemporary clinical Candida and Aspergillus isolates

    DEFF Research Database (Denmark)

    Astvad, K. M.T.; Hare, R. K.; Arendrup, M. C.


    Objective The in vitro activity of isavuconazole was determined for 1677 Candida and 958 Aspergillus isolates from 2012 to 2014 with voriconazole as comparator. Methods Aspergillus isolates were screened for resistance using azole-agar. Aspergillus isolates that screened positive and all Candida.......03 (≤0.03–4), Candida krusei: 0.06 (≤0.03–0.5), Candida parapsilosis: ≤0.03 (≤0.03–0.06), Candida tropicalis: ≤0.03 (≤0.03 to >4), Saccharomyces cerevisiae (anamorph: Candida robusta): ≤0.03 (≤0.03–0.5). Non-wt isavuconazole/voriconazole MICs were found for C. albicans: 0.8/1.0%, C. dubliniensis: 0...... flavus: 1 (0.5–2), Aspergillus nidulans: ≤0.125 (≤0.125–0.25). Non-wt isavuconazole/voriconazole MICs were found for 13.7/15.2% A. fumigatus, 4.9/0% A. niger and 48.2/22.2% A. terreus. Conclusion Isavuconazole displayed broad in vitro activity, similar to that of voriconazole. Up to 15% of C. glabrata, C...

  7. Mechanisms of resistance to fluconazole in Candida albicans clinical isolates from Iranian HIV-infected patients with oropharyngeal candidiasis. (United States)

    Salari, S; Khosravi, A R; Mousavi, S A A; Nikbakht-Brojeni, G H


    The opportunistic pathogen Candida albicans is the major agent of oropharyngeal candidiasis (OPC) in HIV/AIDS patients. The increased use of fluconazole can lead to the emergence of azole-resistant strains and treatment failures in PLWH (people living with HIV) receiving long-term therapy for OPC. The purpose of this study was to evaluate CDR1, CDR2, MDR1, and ERG11 gene expression in C. albicans clinically isolated from HIV-infected patients in Iran. In this study, we evaluated the molecular mechanisms of azole resistance in 20 fluconazole-resistant C. albicans isolates obtained from Iranian HIV-infected patients with oropharyngeal candidiasis by Real-Time polymerase chain reaction. The overexpression of drug efflux pump CDR1 gene was found to be the major resistance mechanism observed in these isolates. The overexpression of the CDR1 gene correlated strongly with increasing resistance to fluconazole (P<0.05). Additionally, an increased level of mRNA in ERG11 was not observed in any of the tested isolates. Our findings suggested that the CDR1 gene expression to fluconazole resistance in C. albicans is greater than other known genes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Hemolytic activity and production of germ tubes related to pathogenic potential of clinical isolates of Candida albicans

    Directory of Open Access Journals (Sweden)

    Eliana Guilhermetti


    Full Text Available ABSTRACT We assessed the virulence factor profile and in vitro antifungal susceptibility of 27 hospital isolates of C. albicans; 19 of these were from infections (16 urinary and three blood, and the other eight were isolated from sites of colonization (two from hands of health professionals, and six from central venous catheters. The virulence factors assayed were germ tube formation and production of extracellular products (hemolysins, proteinases, and phospholipases. Susceptibility to fluconazole, itraconazole, voriconazole and amphotericin B was determined by E-test. Regarding the virulence factors, the infection isolates produced significantly more hemolysin and germ tubes than the colonization isolates (p<0.05. There were no significant differences in the production of other factors between isolates from the two sources (p>0.05. Amphotericin B showed the lowest minimum inhibitory concentrations for all the isolates. The highest resistance was observed for the azoles, especially in the clinical isolates. These results suggest that the capacity of C. albicans to produce hemolysins and germ tubes may be associated with its pathogenic potential. Colonization isolates may pose a high risk of nosocomial infection, especially when the yeasts show resistance to antifungals. Keywords: Nosocomial infection. Virulence. Candida albicans. Germ tube. Hemolysins. RESUMO Atividade hemolítica e produção de tubos germinativos relacionados ao potencial patogênico de isolados clínicos de Candida albicans O perfil de virulência e o de susceptibilidade in vitro aos antifúngicos de 27 amostras de C. albicans de origem hospitalar foi avaliado, sendo que 19 delas foram isoladas de infecções (16 urinárias e três sanguíneas e as outras oito foram isoladas de colonização (duas de mãos de profissionais da saúde e seis de cateter venoso central. Os seguintes fatores de virulência foram investigados: formação de tubo germinativo e produção de

  9. Mutations in transcription factor Mrr2p contribute to fluconazole resistance in clinical isolates of Candida albicans. (United States)

    Wang, Ying; Liu, Jin-Yan; Shi, Ce; Li, Wen-Jing; Zhao, Yue; Yan, Lan; Xiang, Ming-Jie


    The Candida albicans zinc cluster proteins are a family of transcription factors (TFs) that play essential roles in the development of antifungal drug resistance. Gain-of-function mutations in several TFs, such as Tac1p, Mrr1p and Upc2p, have been previously well documented in azole-resistant clinical C. albicans isolates. Mrr2p (multidrug resistance regulator 2) is a novel TF controlling expression of the ABC transporter gene CDR1 and mediating fluconazole resistance. In this study, the relationship between naturally occurring mutations in MRR2 and fluconazole resistance in clinical C. albicans isolates was investigated. Among a group of 20 fluconazole-resistant clinical C. albicans and 10 fluconazole-susceptible C. albicans, 12 fluconazole-resistant isolates overexpressed CDR1 by at least two-fold compared with the fluconazole-susceptible isolates. Of these 12 resistant isolates, three (C7, C9, C15) contained 11 identical missense mutations, 6 of which occurred only in the azole-resistant isolates. The contribution of these mutations to CDR1 overexpression and therefore to fluconazole resistance was further verified by generating recombinant strains containing the mutated MRR2 gene. The mutated MRR2 alleles from isolate C9 contributed to an almost six-fold increase in CDR1 expression and an eight-fold increase in fluconazole resistance; the missense mutations S466L and T470N resulted in an increase in CDR1 expression of more than two-fold and a four-fold increase in fluconazole resistance. In contrast, the other four missense mutations conferred only two- to four-fold increases in fluconazole resistance, with no significant increase in CDR1 expression. These findings provide some insight into the mechanism by which MRR2 regulates C. albicans multidrug resistance. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  10. Hepatitis E Virus Mutations: Functional and Clinical Relevance


    Tong, Hoang Van; Hoan, Nghiem Xuan; Wang, Bo; Wedemeyer, Heiner; Bock, C.-Thomas; Thirumalaisamy P. Velavan


    Highlights ? HEV causes acute hepatitis and recently comes into focus because of persistent infection in immunocompromised patients. ? HEV variability can be associated with clinical pathogenesis and transmission dynamics. ? Mutations in the HEV genome can influence HEV physiology and virus-host interaction. ? HEV mutations and variability are likely associated with fulminant hepatic failure and chronic hepatitis E. ? The Y1320H and G1634R/K mutations in the RdRp domain contribute to antivira...

  11. Corona mortis: an anatomical variation with clinical relevance. Case report.

    Directory of Open Access Journals (Sweden)

    Guillermo Adrián Rivera-Cardona


    Full Text Available The obturator artery is one of the parietal branches arising from the internal iliac artery, the anatomical variation from which this artery originates is called “The corona mortis”, generally from the external iliac artery or the inferior epigastric artery. This finding was observed bilaterally in a male cadaver during a pelvis dissection. Clinical consideration of the anatomical variation in the obturator artery, during surgical procedures, is of great importance due to the risk of pelvic hemorrhage.

  12. Relevance of guideline-based ICD indications to clinical practice

    Directory of Open Access Journals (Sweden)

    Nora Al-Jefairi


    Guidelines on ICD indications have been proposed by American and European scientific societies since a number of years, based upon trials and expert opinion. In the context of variable economic and political constraints, it is questionable whether these guidelines may be applied to all settings. This review discusses the guideline-based indications, critically examines their applicability to clinical practice, and discusses alternatives to ICD therapy.

  13. Clinical relevance of small copy-number variants in chromosomal microarray clinical testing. (United States)

    Hollenbeck, Dana; Williams, Crescenda L; Drazba, Kathryn; Descartes, Maria; Korf, Bruce R; Rutledge, S Lane; Lose, Edward J; Robin, Nathaniel H; Carroll, Andrew J; Mikhail, Fady M


    The 2010 consensus statement on diagnostic chromosomal microarray (CMA) testing recommended an array resolution ≥400 kb throughout the genome as a balance of analytical and clinical sensitivity. In spite of the clear evidence for pathogenicity of large copy-number variants (CNVs) in neurodevelopmental disorders and/or congenital anomalies, the significance of small, nonrecurrent CNVs (<500 kb) has not been well established in a clinical setting. We investigated the clinical significance of all nonpolymorphic small, nonrecurrent CNVs (<500 kb) in patients referred for CMA clinical testing over a period of 6 years, from 2009 to 2014 (a total of 4,417 patients). We excluded from our study patients with benign or likely benign CNVs and patients with only recurrent microdeletions/microduplications <500 kb. In total, 383 patients (8.67%) were found to carry at least one small, nonrecurrent CNV, of whom 176 patients (3.98%) had one small CNV classified as a variant of uncertain significance (VUS), 45 (1.02%) had two or more small VUS CNVs, 20 (0.45%) had one small VUS CNV and a recurrent CNV, 113 (2.56%) had one small pathogenic or likely pathogenic CNV, 17 (0.38%) had two or more small pathogenic or likely pathogenic CNVs, and 12 (0.27%) had one small pathogenic or likely pathogenic CNV and a recurrent CNV. Within the pathogenic group, 80 of 142 patients (56% of all small pathogenic CNV cases) were found to have a single whole-gene or exonic deletion. The themes that emerged from our study are presented in the Discussion section. Our study demonstrates the diagnostic clinical relevance of small, nonrecurrent CNVs <500 kb during CMA clinical testing and underscores the need for careful clinical interpretation of these CNVs.Genet Med 19 4, 377-385.

  14. Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

    Directory of Open Access Journals (Sweden)

    Pignattari Elena


    Full Text Available Abstract Background Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. Objectives To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. Methods The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. Results Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%. Hyperamylasemia was more likely (17% where a microorganism could be identified in the stools (p Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 % and 10/45 (22.2%, respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P Conclusions Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

  15. Cashew Nut Allergy: Clinical Relevance and Allergen Characterisation. (United States)

    Mendes, Cíntia; Costa, Joana; Vicente, António A; Oliveira, Maria Beatriz P P; Mafra, Isabel


    Cashew plant (Anacardium occidentale L.) is the most relevant species of the Anacardium genus. It presents high economic value since it is widely used in human nutrition and in several industrial applications. Cashew nut is a well-appreciated food (belongs to the tree nut group), being widely consumed as snacks and in processed foods by the majority of world's population. However, cashew nut is also classified as a potent allergenic food known to be responsible for triggering severe and systemic immune reactions (e.g. anaphylaxis) in sensitised/allergic individuals that often demand epinephrine treatment and hospitalisation. So far, three groups of allergenic proteins have been identified and characterised in cashew nut: Ana o 1 and Ana o 2 (cupin superfamily) and Ana o 3 (prolamin superfamily), which are all classified as major allergens. The prevalence of cashew nut allergy seems to be rising in industrialised countries with the increasing consumption of this nut. There is still no cure for cashew nut allergy, as well as for other food allergies; thus, the allergic patients are advised to eliminate it from their diets. Accordingly, when carefully choosing processed foods that are commercially available, the allergic consumers have to rely on proper food labelling. In this sense, the control of labelling compliance is much needed, which has prompted the development of proficient analytical methods for allergen analysis. In the recent years, significant research advances in cashew nut allergy have been accomplished, which are highlighted and discussed in this review.

  16. Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance (United States)

    Balucan, Francis S.; Morshed, Syed A.; Davies, Terry F.


    Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum. PMID:23691429

  17. Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance (United States)

    Graeff-Teixeira, Carlos; da Silva, Ana Cristina Arámburu; Yoshimura, Kentaro


    Summary: Eosinophilic meningoencephalitis is caused by a variety of helminthic infections. These worm-specific infections are named after the causative worm genera, the most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Worm parasites enter an organism through ingestion of contaminated water or an intermediate host and can eventually affect the central nervous system (CNS). These infections are potentially serious events leading to sequelae or death, and diagnosis depends on currently limited molecular methods. Identification of parasites in fluids and tissues is rarely possible, while images and clinical examinations do not lead to a definitive diagnosis. Treatment usually requires the concomitant administration of corticoids and anthelminthic drugs, yet new compounds and their extensive and detailed clinical evaluation are much needed. Eosinophilia in fluids may be detected in other infectious and noninfectious conditions, such as neoplastic disease, drug use, and prosthesis reactions. Thus, distinctive identification of eosinophils in fluids is a necessary component in the etiologic diagnosis of CNS infections. PMID:19366917

  18. Osteoprotegerin and Vascular Calcification: Clinical and Prognostic Relevance. (United States)

    Makarović, Sandra; Makarović, Zorin; Steiner, Robert; Mihaljević, Ivan; Milas-Ahić, Jasminka


    Osteoprotegerin (OPG) is a key regulator in bone metabolism, that also has effect in vascular system. Studies suggest that osteoprotegerin is a critical arterial calcification inhibitor, and is released by endothelial cells as a protective mechanism for their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders. That has been shown in studies in vitro and in animal models. The discovery that OPG deficient mice (OPG -/- mice) develop severe osteoporosis and arterial calcification, has led to conclusion that osteoprotegerin might be mulecule linking vascular and bone system. Paradoxically however, clinical trials have shown recently that OPG serum levels is increased in coronary artery disease and correlates with its severity, ischemic cardial decompensation, and future cardiovascular events. Therefore it is possible that osteoprotegerin could have a new function as a potential biomarker in early identification and monitoring patients with cardiovascular disease. Amongst that osteoprotegerin is in association with well known atherosclerosis risc factors: undoubtedly it is proven its relationship with age, smoking and diabetes mellitus. There is evidence regarding presence of hyperlipoproteinemia and increased serum levels of osteoprotegerin. Also the researches have been directed in genetic level, linking certain single nucleotid genetic polymorphisms of osteoprotegerin and vascular calcification appearance. This review emphasises multifactorial role of OPG, presenting numerous clinical and experimental studies regarding its role in vascular pathology, suggesting a novel biomarker in cardiovascular diseases, showing latest conclusions about this interesting topic that needs to be further explored.

  19. What is the clinical relevance of different lung compartments? (United States)


    The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense. All these compartments are connected but the functional network is not yet fully understood. A better knowledge of the complex interactions could improve diagnosis and therapy, or enable preventive approaches of local immunization. PMID

  20. What is the clinical relevance of different lung compartments?

    Directory of Open Access Journals (Sweden)

    Pabst Reinhard


    Full Text Available Abstract The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 – the bronchoalveolar lavage (BAL, which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 – bronchus-associated lymphoid tissue (BALT: In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 – conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL. This again is also accessible via bronchoscopy. Compartment 4 – draining lymph nodes/Compartment 5 – lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments – lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 – the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 – periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense. All these compartments are connected but the functional network is not yet fully understood. A better knowledge of the complex interactions could improve diagnosis and therapy, or enable preventive approaches

  1. Myocardial ischaemia in systemic lupus erythematosus: detection and clinical relevance. (United States)

    Płazak, Wojciech; Gryga, Krzysztof; Sznajd, Jan; Pasowicz, Mieczysław; Musiał, Jacek; Podolec, Piotr


    Severe cardiovascular complications are among the most important causes of mortality in systemic lupus erythematosus (SLE) patients. To assess the usefulness of echocardiography, ECG, and coronary artery calcium scoring (CACS) in the detection of myocardial ischaemia in SLE patients compared to single photon emission computerised tomography (SPECT) and to assess their five-year follow-up. In 50 consecutive SLE patients (mean age 39.2 ± 12.9 years, 90% female), clinical assessment, resting and exercise ECG and echocardiography, multidetector computed tomography - based CACS and SPECT studies (Tc-99m sestamibi) were performed. Patients were then followed for five years. SPECT revealed perfusion defects in 25 (50%) patients; persistent defects in 18 (36%) and exercise-induced defects in seven (14%) subjects. No typical ischaemic heart disease clinical symptoms, signs of ischaemia in resting ECG, or left ventricular contractility impairment in echocardiography were observed. Signs of ischaemia in exercise ECG were found in 17 (34%) patients. The CACS ranged from 1 to 843.2 (median 23.15), and coronary calcifications were observed in 12 (24%) patients. Compared to the SPECT study, exercise ECG had 68% sensitivity and 100% specificity in detecting myocardial ischaemia, while CACS had only 28% sensitivity and 58% specificity. During follow-up, one patient who showed myocardial perfusion defects and the highest calcium score (843.2) at baseline, developed CCS II class symptoms of myocardial ischaemia. Coronary angiography was not performed because of severe anaemia; the patient died three months later. In two other patients with perfusion defects and calcium deposits at baseline, CCS I class symptoms were observed; coronary angiography showed only thin calcified coronary plaques that were haemodynamically insignificant. In about half of relatively young, mostly female, SLE patients, SPECT shows myocardial perfusion defects, with coronary calcifications present in one

  2. Hepatitis E Virus Mutations: Functional and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hoang van Tong


    Full Text Available Hepatitis E virus (HEV infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance.

  3. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis

    DEFF Research Database (Denmark)

    De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos


    Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceed......Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS...... in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may...

  4. Epigenetics in prostate cancer: biologic and clinical relevance. (United States)

    Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F


    Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  5. Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Ronen Ben-Ami


    Full Text Available Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance. We used population analysis profiling (PAP to assess fluconazole heteroresistance (FLCHR and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6% of 52 fluconazole-sensitive clinical C. glabrata isolates met accepted dichotomous criteria for FLCHR. However, quantitative grading of FLCHR by using the area under the PAP curve (AUC revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1 genes, encoding ATP-binding cassette (ABC transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLCHRC. glabrata was recovered more frequently than nonheteroresistant C. glabrata from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%, P = 0.029. Phylogenetic analysis revealed some phenotypic clustering but also variations in FLCHR within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of C. glabrata for persistent infection and the emergence of breakthrough resistance to fluconazole.

  6. Clinical relevance of the STOPP/START criteria in hip fracture patients. (United States)

    Lönnbro, Johan; Wallerstedt, Susanna M


    The aim of this study was to investigate the clinical relevance of potentially inappropriate medications (PIMs), identified by the STOPP criteria, and potential prescribing omissions (PPOs), identified by the START criteria, and to identify predictors for clinically relevant PIMs and PPOs. The STOPP and START criteria were applied on the medication lists of 200 older hip fracture patients, consecutively recruited to a randomized controlled study in 2009. For each identified PIM and/or PPO, the clinical relevance was assessed at the individual level, using medical records from both hospital and primary care as well as data collected in the original study. A total of 555 PIMs/PPOs were identified in 170 (85%) patients (median age: 85 years, 67% female), 298 (54%) of which, in 141 (71%) patients, were assessed as clinically relevant. A greater proportion of PIMs than PPOs were clinically relevant: 71% (95% CI: 66%; 76%) vs. 32% (27%; 38%). A greater proportion of PPOs than PIMs could not be assessed with available information: 38% (32%; 44%) vs. 22% (17%; 27%). Number of drugs and multidose drug dispensing, but not age, sex, cognition, or nursing home residence, were associated with ≥1 clinically relevant PIMs/PPOs. The present study illustrates that one in two PIMs/PPOs identified by the STOPP/START criteria is clearly clinically relevant, PIMs being clinically relevant to a greater extent than PPOs. Based on available information, the clinical relevance could not be determined in a non-negligible proportion of PIMs/PPOs. Number of drugs and multidose drug dispensing were associated with ≥1 clinically relevant PIMs/PPOs.

  7. Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes. (United States)

    King, Paula; Pham, Long K; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca; Forsyth, R Allyn


    We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile.

  8. Uterine fibroid vascularization and clinical relevance to uterine fibroid embolization. (United States)

    Pelage, Jean-Pierre; Cazejust, Julien; Pluot, Etienne; Le Dref, Olivier; Laurent, Alexandre; Spies, James B; Chagnon, Sophie; Lacombe, Pascal


    Embolization has become a first-line treatment for symptomatic uterine fibroid tumors. Selective catheterization and embolization of both uterine arteries, which are the predominant source of blood flow to fibroid tumors in most cases, is the cornerstone of treatment. Although embolization for treatment of uterine fibroid tumors is widely accepted, great familiarity with the normal and variant pelvic arterial anatomy is needed to ensure the safety and success of the procedure. The uterine artery classically arises as a first or second branch of the anterior division of the internal iliac artery and is usually dilated in the presence of a uterine fibroid tumor. Angiography is used for comprehensive pretreatment assessment of the pelvic arterial anatomy; for noninvasive evaluation, Doppler ultrasonography, contrast material-enhanced magnetic resonance (MR) imaging, and MR angiography also may be used. After the uterine artery is identified, selective catheterization should be performed distal to its cervicovaginal branch. For targeted embolization of the perifibroid arterial plexus, injection of particles with diameters larger than 500 mum is generally recommended. Excessive embolization may injure normal myometrium, ovaries, or fallopian tubes and lead to uterine necrosis or infection or to ovarian failure. Incomplete treatment or additional blood supply to the tumor (eg, via an ovarian artery) may result in clinical failure. The common postembolization angiographic end point is occlusion of the uterine arterial branches to the fibroid tumor while antegrade flow is maintained in the main uterine artery. Copyright RSNA, 2005.

  9. Metrics and clinical relevance of percutaneous penetration and lateral spreading. (United States)

    Vieille-Petit, Aline; Blickenstaff, Nicholas; Coman, Garrett; Maibach, Howard


    Percutaneous penetration of urea in vivo in man has been documented. If urea can penetrate the skin, it may also move laterally. Lateral spreading of topical substances leads to unpredictable penetration dynamics and increased skin surface area exposure. The ability of urea, a low molecular-weight hydrophilic model, to penetrate the stratum corneum (SC) and spread outside the application site was investigated in vitro using tape stripping with spectroscopy. The parameters investigated were the following: time between urea application and tape stripping, formulations containing urea and use of a petrolatum-covered ring barrier around the marked application area. The percentage of urea was determined in and around the application site. The spreading of topically applied urea to neighboring areas occurred and was time but not formulation dependent. A significant difference between protocols with and without the petrolatum ring was observed. These results suggest the clinical importance of lateral spreading, occurring predominately on the skin surface. SC thickness varies between anatomical sites, predisposing areas such as the face and scalp margins to increased percutaneous penetration of topical products. The use of a protective petrolatum ring can inhibit lateral spreading of hair dye in individuals allergic to hair dye, limit systemic absorption and increase accuracy when assessing penetration dynamics. © 2014 S. Karger AG, Basel.

  10. Review of Post Ischemic Stroke Imaging and Its Clinical Relevance. (United States)

    Yeo, Leonard L L; Tan, Benjamin Y Q; Andersson, Tommy


    In this day and age, multiple imaging modalities are available to the stroke physician in the post-treatment phase.The practical challenge for physicians who treat stroke is to evaluate the pros and cons of each technique and select the best choice for the situation. The choice of imaging modality remains contentious at best and varies among different institutions and centres. This is no simple task an there are many factors to consider, including the differential diagnosis which need to be evaluated, the availability and reliability of the imaging technique and time and expertise required to perform and interpret the scanning. Other ancillary competing interest also come into play such as the financial cost of the modality, the requirement for patient monitoring during the imaging procedure and patient comfort. In an effort to clear some of the ambiguity surrounding this topic we present some of the current techniques in use and others, which are still in the realm of research and have not yet transitioned into clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Clinical Relevance of Intraperitoneal Pressure in Peritoneal Dialysis Patients. (United States)

    Castellanos, Loreley Betancourt; Clemente, Esther Ponz; Cabañas, Conchita Blasco; Parra, Dolors Marquina; Contador, Mabel Bolós; Morera, Juan Carlos Oliva; Daly, Jaume Almirall


    Intraperitoneal pressure (IPP) in peritoneal dialysis (PD) increases in sitting and upright positions and is related to some individual characteristics. Adverse effects can appear with IPP > 20 cm H2O. Few studies about peritoneal transport or abdominal wall problems have directly measured IPP. We measured IPP in our prevalent PD patients to identify the clinical factors related to its variability and its possible association with peritoneal transport and abdominal wall complications. We performed a retrospective, observational study of our stable PD patients. Intraperitoneal pressure was measured using the Durand's method in supine, sitting, and upright position. Forty-nine patients were included, 70% males, mean age 61.1 ± 15 years, body mass index (BMI) 27.9 ± 5.2 kg/m(2). The mean of supine IPP was 18.0 ± 4.4 cm H2O. Intraperitoneal pressure in sitting and upright positions were similar and higher than in supine. Supine IPP showed a positive correlation with BMI (p < 0.0005) and comorbidity (p < 0.05). A multivariate linear regression analysis showed that BMI and comorbidity (p < 0.005) had a positive correlation with IPP; time on PD and daily total ultrafiltration (UF) (p < 0.005) showed a negative correlation. Patients with an IPP ≥ 20 cm H2O had more hernias (35% vs 17%) and leakages (21% vs 8%) without statistical significance. Our supine IPPs were higher than others published in adults. Intraperitoneal pressure has an individual value associated with body size. Greater IPP was correlated with lower daily total UF and more hernias and leakages. The measurement of IPP is a simple technique and can help with PD prescription, especially in obese patients. Copyright © 2017 International Society for Peritoneal Dialysis.

  12. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance (United States)

    Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio


    Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal

  13. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ines Bucci


    Full Text Available Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH receptor (TSHR antibodies (TRAbs are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs, blocking (TBAbs, or neutral (N-TRAbs depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and

  14. [Ibogaine - structure, influence on human body, clinical relevance]. (United States)

    Zdrojewicz, Zygmunt; Kuszczak, Bartłomiej; Olszak, Natalia


    Ibogaine is a natural chemical compound, which belongs to the indole alkaloid family. It can be naturally found within the root bark of african plant Tabernanthe iboga. Ibogaine plays a significant role among tribal cultures. Ibogaine, in small amount, causes reduction of hunger, thirst and exhaustion. In bigger amount, however, it can cause intensive visions. Other effects include reduction or complete disappearance of absitnence symptoms visible in people addicted to the nicotine, alcohol, methamphetamine, cocaine or opioids, what has been scientifically proven after the tests on animals and small groups of people. After oral application, 80% of ibogaine is subjected to the Odemethylation into noribogaine; main catalyzing enzyme is cytochrome CYP2D6. Research suggests, that ibogaine acts in many places within central nervous system. NMDA receptors seem to play main role in its anti-addiction properties. It is important to mention the side effects of the compound, which are cardiotoxicity and neurotoxicity, what makes it harder to use its beneficial properties. Because of this, Ibogaine is included among the dangerous substance. However, there are a few clinics in the world which specializes in the use of the compound in order to interrupt the sypmtoms acute opioid withdrawal syndrome as well as a substance benficial in curing other addictions. There is more hope with synthetic derivatives of ibogaine, which although are less toxic still keep their anti-addiction properties. The aim is to collect the available knowledge related to the structure and effects on human body of alkaloid Tabernanthe iboga and consider the possibility of commercial medical use. © 2016 MEDPRESS.

  15. Development of a novel, simple and rapid molecular identification system for clinical Candida species

    NARCIS (Netherlands)

    Deak, R.; Bodia, L.; Aarts, H.J.M.; Maraz, A.


    Identification of clinical yeast isolates causing candidiasis is routinely performed by commercial yeast identification systems based on biochemical, morphological and physiological tests. These systems require 3-5 days and the proportion of identifications that are incorrect is high. Our novel and

  16. Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence.

    LENUS (Irish Health Repository)

    McManus, Brenda A


    Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral Candida populations from 16 Irish APECED patients, who comprise approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of Candida isolates. Patients attended between one and four clinical evaluations over a 5-year period, providing oral rinses and\\/or oral swab samples each time. Candida was recovered from 14\\/16 patients, and Candida albicans was the only Candida species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of Candida infection at 7\\/22 (32%) clinical assessments. Multilocus sequence typing analysis of C. albicans isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and\\/or fluconazole susceptibility were identified in a further 3\\/16 patients, in each case correlating with the upregulation of CDR- and MDR-encoded efflux pumps. Mutations were also identified in the ERG11 and the TAC1 genes of isolates from these four patients; some of these mutations have previously been associated with azole resistance. The findings suggest that alternative Candida treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-Candida therapy.

  17. Effects of Fluconazole on the Secretome, the Wall Proteome, and Wall Integrity of the Clinical Fungus Candida albicans ▿ † (United States)

    Sorgo, Alice G.; Heilmann, Clemens J.; Dekker, Henk L.; Bekker, Martijn; Brul, Stanley; de Koster, Chris G.; de Koning, Leo J.; Klis, Frans M.


    Fluconazole is a commonly used antifungal drug that inhibits Erg11, a protein responsible for 14α-demethylation during ergosterol synthesis. Consequently, ergosterol is depleted from cellular membranes and replaced by toxic 14α-methylated sterols, which causes increased membrane fluidity and drug permeability. Surface-grown and planktonic cultures of Candida albicans responded similarly to fluconazole at 0.5 mg/liter, showing reduced biomass formation, severely reduced ergosterol levels, and almost complete inhibition of hyphal growth. There was no evidence of cell leakage. Mass spectrometric analysis of the secretome showed that its composition was strongly affected and included 17 fluconazole-specific secretory proteins. Relative quantification of 14N-labeled query walls relative to a reference standard mixture of 15N-labeled yeast and hyphal walls in combination with immunological analysis revealed considerable fluconazole-induced changes in the wall proteome as well. They were, however, similar for both surface-grown and planktonic cultures. Two major trends emerged: (i) decreased incorporation of hypha-associated wall proteins (Als3, Hwp1, and Plb5), consistent with inhibition of hyphal growth, and (ii) increased incorporation of putative wall repair-related proteins (Crh11, Pga4, Phr1, Phr2, Pir1, and Sap9). As exposure to the wall-perturbing drug Congo red led to a similar response, these observations suggested that fluconazole affects the wall. In keeping with this, the resistance of fluconazole-treated cells to wall-perturbing compounds decreased. We propose that fluconazole affects the integrity of both the cellular membranes and the fungal wall and discuss its potential consequences for antifungal therapy. We also present candidate proteins from the secretome for clinical marker development. PMID:21622905

  18. Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients. (United States)

    Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring


    Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

  19. Clinical decision support systems differ in their ability to identify clinically relevant drug interactions of immunosuppressants in kidney transplant patients. (United States)

    Amkreutz, J; Koch, A; Buendgens, L; Trautwein, C; Eisert, A


    In kidney transplant patients, clinically relevant drug-drug interactions (DDIs) with immunosuppressants potentially lead to serious adverse drug events (ADEs). The aim of this study was (i) to show that five clinical decision support systems (CDSSs) differ in their ability to identify clinically relevant potential DDIs (pDDIs) of immunosuppressants in kidney transplant patients and (ii) to compare CDSSs in terms of their ability to identify clinically relevant pDDIs in this context. All pDDIs being possible between nine immunosuppressants and 234 comedication drugs were identified for 264 intensive care unit (ICU) kidney transplant patients from 1999 to 2010. For pDDI identification, five CDSSs were used: DRUG-REAX® , ID PHARMA CHECK® , Lexi-Interact, mediQ and Meona. PDDIs from high severity categories were defined as clinically relevant. Classification of pDDIs as clinically relevant/non-clinically relevant by a clinical pharmacist using Stockley's Drug Interactions was employed as benchmark. We analysed inter-rater agreement, sensitivity, specificity, positive predictive value and negative predictive value. Clinical decision support systems generated a total of 759 pDDI alerts. A total of 240 pDDI alerts were in high severity categories. A total of 391 different pDDIs were identified. Only 5% (n = 35) of different pDDIs were identified by all CDSSs. A total of 49 pDDIs were classified as clinically relevant by clinical pharmacists' rating using Stockley's Drug Interactions. Meona (0·72) has the highest inter-rater agreement with the benchmark for clinically relevant pDDIs. ID PHARMA CHECK® and mediQ show highest sensitivities (0·74, respectively). Meona has the highest specificity (0·99) and positive predictive value (0·89). Five CDSSs differ in their ability to identify clinically relevant pDDIs of immunosuppressants in kidney transplant patients. Data may assist in selecting CDSSs for kidney transplant patients in the ICU. Using CDSSs to identify

  20. Reproducibility and clinical relevance of quantitative EEG parameters in cerebral ischemia: A basic approach.

    NARCIS (Netherlands)

    Sheorajpanday, Rishi V.A.; Nagels, Guy; Weeren, Arie J.T.M.; van Putten, Michel Johannes Antonius Maria; de Deyn, Peter P.


    Objective To investigate reproducibility and clinical relevance of quantitative EEG parameters in ischemic cerebrovascular disease. Methods EEG was recorded in 31 patients suffering from subacute ischemic cerebrovascular disease. Ten age-matched control subjects were included as a reference group.

  1. Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence. (United States)

    Ben-Ami, Ronen; Zimmerman, Offer; Finn, Talya; Amit, Sharon; Novikov, Anna; Wertheimer, Noa; Lurie-Weinberger, Mor; Berman, Judith


    Candida glabrata causes persistent infections in patients treated with fluconazole and often acquires resistance following exposure to the drug. Here we found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug response (heteroresistance). We used population analysis profiling (PAP) to assess fluconazole heteroresistance (FLC(HR)) and to ask if it is a binary trait or a continuous phenotype. Thirty (57.6%) of 52 fluconazole-sensitive clinical C. glabrata isolates met accepted dichotomous criteria for FLC(HR) However, quantitative grading of FLC(HR) by using the area under the PAP curve (AUC) revealed a continuous distribution across a wide range of values, suggesting that all isolates exhibit some degree of heteroresistance. The AUC correlated with rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1 genes, encoding ATP-binding cassette (ABC) transmembrane transporters, implying that HetR populations exhibit higher levels of drug efflux. Highly FLC(HR) C. glabrata was recovered more frequently than nonheteroresistant C. glabrata from hematogenously infected immunocompetent mice following treatment with high-dose fluconazole (45.8% versus 15%, P = 0.029). Phylogenetic analysis revealed some phenotypic clustering but also variations in FLC(HR) within clonal groups, suggesting both genetic and epigenetic determinants of heteroresistance. Collectively, these results establish heteroresistance to fluconazole as a graded phenotype associated with ABC transporter upregulation and fluconazole efflux. Heteroresistance may explain the propensity of C. glabrata for persistent infection and the emergence of breakthrough resistance to fluconazole. Heteroresistance refers to variability in the response to a drug within a clonal cell population. This phenomenon may have crucial importance for the way we look at antimicrobial resistance, as heteroresistant strains are not detected by standard laboratory susceptibility testing

  2. Clinical relevance of the STOPP/START criteria in hip fracture patients


    L?nnbro, Johan; Wallerstedt, Susanna M


    Purpose The aim of this study was to investigate the clinical relevance of potentially inappropriate medications (PIMs), identified by the STOPP criteria, and potential prescribing omissions (PPOs), identified by the START criteria, and to identify predictors for clinically relevant PIMs and PPOs. Methods The STOPP and START criteria were applied on the medication lists of 200 older hip fracture patients, consecutively recruited to a randomized controlled study in 2009. For each identified PI...

  3. Clinical Relevance of Nontuberculous Mycobacteria Isolated from Sputum in a Gold Mining Workforce in South Africa: An Observational, Clinical Study


    van Halsema, CL; Chihota, VN; Gey van Pittius, NC; Fielding, KL; Lewis, JJ; van Helden, PD; Churchyard, GJ; Grant, AD


    Background. The clinical relevance of nontuberculous mycobacteria (NTM), detected by liquid more than solid culture in sputum specimens from a South African mining workforce, is uncertain. We aimed to describe the current spectrum and relevance of NTM in this population. Methods. An observational study including individuals with sputum NTM isolates, recruited at workforce tuberculosis screening and routine clinics. Symptom questionnaires were administered at the time of sputum collection and ...

  4. The widely used ATB FUNGUS 3 automated readings in China and its misleading high MICs of Candida spp. to azoles: challenges for developing countries' clinical microbiology labs.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available The rapid development in the clinical microbiology diagnostic assays presents more challenges for developing countries than for the developed world, especially in the area of test validation before the introduction of new tests. Here we report on the misleading high MICs of Candida spp. to azoles using the ATB FUNGUS 3 (bioMérieux, La Balme-les Grottes, France with automated readings in China to highlight the dangers of introducing a diagnostic assay without validation. ATB FUNGUS 3 is the most commonly used commercial antifungal susceptibility testing method in China. An in-depth analysis of data showed higher levels of resistance to azoles when ATB FUNGUS 3 strips were read automatically than when read visually. Based on this finding, the performance of ATB FUNGUS 3, read both visually and automatically, was evaluated by testing 218 isolates of five clinically important Candida species, using broth microdilution (BMD following CLSI M27-A3 as the gold-standard. The overall essential agreement (EA between ATB visual readings and BMD was 99.1%. In contrast, the ATB automated readings showed higher discrepancies with BMD, with overall EA of 86.2%, and specifically lower EA was observed for fluconazole (80.7%, voriconazole (77.5%, and itraconazole (73.4%, which was most likely due to the trailing effect of azoles. The major errors in azole drug susceptibilities by ATB automated readings is a concern in China that can result in misleading clinical antifungal drug selection and pseudo high rates of antifungal resistance. Therefore, the ATB visual reading is generally recommended. In the meantime, we propose a practical algorithm to be followed for ATB FUNGUS 3 antifungal susceptibility for Candida spp. before the improvement in the automated reading system.

  5. Postantifungal effect of caspofungin against the Candida albicans and Candida parapsilosis clades. (United States)

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo


    Killing and postantifungal effects could be relevant for the selection of optimal dosing schedules. This study aims to compare time-kill and postantifungal effects with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis, Candida orthopsilosis) clades. In the postantifungal effect experiments, strains were exposed to caspofungin for 1 h at concentrations 0.12-8 μg/mL. Time-kill experiments were conducted at the same concentrations. Caspofungin exhibited a significant and prolonged postantifungal effect (>37 h) with 2 μg/mL against the most strains of C. albicans clade. Against the C. parapsilosis clade, the postantifungal effect was albicans, C. dubliniensis and C. metapsilosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Interlaboratory variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? (United States)

    Espinel-Ingroff, A; Arendrup, M C; Pfaller, M A; Bonfietti, L X; Bustamante, B; Canton, E; Chryssanthou, E; Cuenca-Estrella, M; Dannaoui, E; Fothergill, A; Fuller, J; Gaustad, P; Gonzalez, G M; Guarro, J; Lass-Flörl, C; Lockhart, S R; Meis, J F; Moore, C B; Ostrosky-Zeichner, L; Pelaez, T; Pukinskas, S R B S; St-Germain, G; Szeszs, M W; Turnidge, J


    Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp., epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.

  7. Pre-clinical development of antifungal susceptibility test methods for the testing of the novel antifungal agent E1210 versus Candida: comparison of CLSI and European Committee on Antimicrobial Susceptibility Testing methods. (United States)

    Pfaller, Michael A; Watanabe, Naoaki; Castanheira, Mariana; Messer, Shawn A; Jones, Ronald N


    To compare European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI broth microdilution (BMD) methods for testing the novel antifungal E1210 against a recent collection of 102 clinical isolates of Candida spp. Candida isolates (102) were tested by CLSI and EUCAST methods; 21 Candida albicans, 20 Candida glabrata, 25 Candida parapsilosis, 24 Candida tropicalis and 12 Candida krusei, including echinocandin- and azole-resistant isolates. CLSI and EUCAST MIC endpoints of 50% and 100% inhibition were determined using visual reading at 24 and 48 h of incubation and spectrophotometric reading at 24 h of incubation, respectively. E1210 CLSI MIC results ranged from ≤0.008 to only 1 mg/L (excluding C. krusei) depending on species, duration of incubation and endpoint criteria (EC). E1210 was not active against C. krusei (MIC(50) >16 mg/L). Overall essential agreement (EA; ±2 doubling dilutions) between the 24 and 48 h CLSI readings was 100% and 97.6% using the 50% and 100% inhibition EC, respectively. Slightly more trailing growth at 48 h was observed with the 100% inhibition EC. Comparison of the 50% and 100% endpoints at 24 h of incubation showed an overall EA of 100%. Comparison of CLSI and EUCAST read at 24 h of incubation and either 50% or 100% inhibition revealed an EA of 97.8% using the 50% inhibition EC and 88.9% using the 100% inhibition EC. E1210 was found to have potent in vitro activity against Candida spp. when tested by both CLSI and EUCAST BMD methods, with the highest overall EA (97.8%) obtained when E1210 MIC results were read after 24 h of incubation using a partial inhibition EC.

  8. The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence

    DEFF Research Database (Denmark)

    Gräs, Søren; Lose, Gunnar


    Stress urinary incontinence is a common disorder affecting the quality of life for millions of women worldwide. Effective surgical procedures involving synthetic permanent meshes exist, but significant short- and long-term complications occur. Cell-based therapy using autologous stem cells...... regulatory demands. The influence on the cost effectiveness, the clinical relevance and the future perspectives of the present clinical approach are discussed....

  9. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G


    BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was ...

  10. Self-Esteem and Dimensions of Clinically Relevant Behavior Among Ten Year Olds. (United States)

    Starr, Philip; Pearman, William A.

    Although self-concept has been linked with many behavioral variables, most studies do not deal with dependent variables which would provide an understanding of such clinically relevant behaviors as sociability, aggression, activity level, somatization, inhibition, and sleep disturbance. The relationship between self-esteem and clinically relevant…

  11. Clinical relevance of Mycobacterium chelonae-abscessus group isolation in 95 patients.

    NARCIS (Netherlands)

    Ingen, J. van; Zwaan, R. de; Dekhuijzen, P.N.R.; Boeree, M.J.; Soolingen, D. van


    OBJECTIVES: To determine the clinical relevance of Mycobacterium chelonae-abscessus group isolation from clinical samples. METHODS: We retrospectively reviewed medical files of all patients from whom these mycobacteria were isolated between January 1999 and January 2005 and re-identified the

  12. Contact allergy to colophony. Clinical and experimental studies with emphasis on clinical relevance. (United States)

    Färm, G


    Colophony--also called rosin--is a material obtained from coniferous trees. It is used widely in many products, particularly because of its good tackifying properties. Colophony is also used in paper sizing to increase water resistance. Colophony may cause contact allergy, and around 5% of Swedish dermatitis patients show allergic reactions to colophony at patch testing. There are many case reports of colophony in different products causing contact dermatitis. Often, however, the clinical relevance of a positive patch-test reaction to colophony is difficult to evaluate. The principal aims of the present thesis were to study the prevalence of contact allergy to colophony and of skin disease in individuals with an occupational exposure to colophony; to study the prognosis of dermatitis in colophony-sensitive subjects, and to investigate the outcome of repeated open applications of colophony, thereby trying to elucidate the clinical relevance of contact allergy to colophony. Employees of a tall-oil rosin (colophony) factory (n = 180), and of an opera company where colophony was used in dancers' rosin, mascara and wig glues (n = 132), were interviewed, examined and patch tested. 3.9% and 2% of these two groups respectively had a positive patch test to colophony. More than every fourth participant showed some kind of skin disease, but only few cases were related to work. Eighty-three patients with previously diagnosed contact allergy to colophony were followed-up 72% showed a positive patch-test reaction to colophony at re-testing. Around one third had hand eczema. There was no significant correlation between colophony exposure and current hand eczema. Adhesive bandages containing colophony and zinc oxide (ZnO), colophony and mixes of colophony and ZnO, were tested in 7 colophony-sensitive subjects to see whether addition of zinc oxide inhibited elicitation of allergic dermatitis to colophony, which has been proposed. No difference in reactivity between colophony and

  13. In vitro antifungal activity of fluconazole and voriconazole against non-Candida yeasts and yeast-like fungi clinical isolates. (United States)

    Mandras, Narcisa; Roana, Janira; Scalas, Daniela; Fucale, Giacomo; Allizond, Valeria; Banche, Giuliana; Barbui, Anna; Li Vigni, Nicolò; Newell, Vance A; Cuffini, Anna Maria; Tullio, Vivian


    The risk of opportunistic infections caused by non-Candida yeasts and yeast-like fungi is increasingly common, mainly in immunocompromised patients. Appropriate first-line therapy has not been defined and standardized, mainly due to the low number of cases reported. To improve empirical treatment guidelines, we describe the susceptibility profile to fluconazole and voriconazole of 176 non-Candida yeasts and yeast-like fungi collected from hospitals in Piedmont, North West Italy from January 2009 to December 2013. The results showed that most isolates are susceptible to voriconazole (94%), but less susceptible to fluconazole (78%), suggesting that voriconazole could be used as first-line therapy in infections caused by these fungi.

  14. Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

    Directory of Open Access Journals (Sweden)

    Fábio Silvestre Ataides


    Full Text Available AbstractINTRODUCTION:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis , and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin.METHODS:Differentiation of C. parapsilosis complex species was performed by amplification of the secondary alcohol dehydrogenase (SADH gene and digestion by the restriction enzyme Ban I. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing.RESULTS:Among the 87 isolates, 78 (89.7% were identified as C. parapsilosis sensu stricto , five (5.7% were identified as C. orthopsilosis , and four (4.6% were identified as C. metapsilosis . Analysis of antifungal susceptibility showed that C. parapsilosis sensu strictoisolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu strictoisolates and one C. metapsilosis isolate were susceptible to fluconazole in a dose-dependent manner.CONCLUSIONS:We reported the first molecular identification of C. parapsilosiscomplex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profiles, the primary susceptibility of this species was to caspofungin.

  15. Candida Immunity

    Directory of Open Access Journals (Sweden)

    Julian R. Naglik


    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  16. [Changes in clinically relevant goals and therapy outcome: a study with inpatients undergoing cognitive behavioral therapy]. (United States)

    Berking, Matthias; Grosse Holtforth, Martin; Jacobi, Claus


    According to the consistency theory clinically relevant goals, as explicated by Grosse Holtforth and Grawe, play a prominent role in the development, maintenance and therapy of psychological disorders. Thus effective psychotherapies should "normalize" the subjective importance of these goals. These changes should be positively associated with the success of psychotherapy. To test these assumptions, clinically relevant goals of 64 inpatients undergoing cognitive behavioral therapy were assessed by the Inventory of Approach and Avoidance Goals (German: Fragebogen zur Analyse motivationaler Schemata, FAMOS) before and after therapy. Results show effects of normalization, as expected, especially on scales associated with psychopathology in former studies.

  17. Clinical relevance of studies on the accuracy of visual inspection for detecting caries lesions

    DEFF Research Database (Denmark)

    Gimenez, Thais; Piovesan, Chaiana; Braga, Mariana M


    Although visual inspection is the most commonly used method for caries detection, and consequently the most investigated, studies have not been concerned about the clinical relevance of this procedure. Therefore, we conducted a systematic review in order to perform a critical evaluation considering...... the clinical relevance and methodological quality of studies on the accuracy of visual inspection for assessing caries lesions. Two independent reviewers searched several databases through July 2013 to identify papers/articles published in English. Other sources were checked to identify unpublished literature...

  18. Bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei

    DEFF Research Database (Denmark)

    Kaldau, Niels Christian; Brorson, Stig; Jensen, Poul Einar


    We present a case of bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei, and review the literature on Candida osteomyelitis.......We present a case of bilateral polymicrobial osteomyelitis with Candida tropicalis and Candida krusei, and review the literature on Candida osteomyelitis....

  19. Ag(I camphorimine complexes with antimicrobial activity towards clinically important bacteria and species of the Candida genus.

    Directory of Open Access Journals (Sweden)

    João M S Cardoso

    Full Text Available The present work follows a previous report describing the antibacterial activity of silver camphorimine complexes of general formula [Ag(NO3L]. The synthesis and demonstration of the antifungal and antibacterial activity of three novel [Ag(NO3L] complexes (named 1, 2 and 3 is herein demonstrated. This work also shows for the first time that the previously studied complexes (named 4 to 8 also exert antifungal activity. The antibacterial activity of complexes was evaluated against Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia contaminans and Escherichia coli strains, while antifungal activity was tested against the Candida species C. albicans, C. glabrata, C. parapsilosis and C. tropicalis. The antimicrobial activity of the complexes ranged from very high (complex 4 to moderate (complex 6 or low (complex 8, depending on the structural and electronic characteristics of the camphorimine ligands. Notably, the highest antibacterial and anti-Candida activities do not coincide in the same complex and in some cases they were even opposite, as is the case of complex 4 which exhibits a high anti-bacterial and low antifungal activity. These distinct results suggest that the complexes may have different mechanisms against prokaryotic and eukaryotic cells. The antifungal activity of the Ag(I camphorimine complexes (in particular of complex 1 was found to be very high (MIC = 2 μg/mL against C. parapsilosis, being also registered a prominent activity against C. tropicalis and C. glabrata. None of the tested compounds inhibited C. albicans growth, being this attributed to the ability of these yeast cells to mediate the formation of less toxic Ag nanoparticles, as confirmed by Scanning Electron Microscopy images. The high antibacterial and anti-Candida activities of the here studied camphorimine complexes, especially of complexes 1 and 7, suggests a potential therapeutic application for these compounds.

  20. Candida Pneumonia in Intensive Care Unit? (United States)

    Schnabel, Ronny M.; Linssen, Catharina F.; Guion, Nele; van Mook, Walther N.; Bergmans, Dennis C.


    It has been questioned if Candida pneumonia exists as a clinical entity. Only histopathology can establish the definite diagnosis. Less invasive diagnostic strategies lack specificity and have been insufficiently validated. Scarcity of this pathomechanism and nonspecific clinical presentation make validation and the development of a clinical algorithm difficult. In the present study, we analyze whether Candida pneumonia exists in our critical care population. We used a bronchoalveolar lavage (BAL) specimen database that we have built in a structural diagnostic approach to ventilator-associated pneumonia for more than a decade consisting of 832 samples. Microbiological data were linked to clinical information and available autopsy data. We searched for critically ill patients with respiratory failure with no other microbiological or clinical explanation than exclusive presence of Candida species in BAL fluid. Five cases could be identified with Candida as the likely cause of pneumonia. PMID:25734099

  1. Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species (United States)

    Whaley, Sarah G.; Berkow, Elizabeth L.; Rybak, Jeffrey M.; Nishimoto, Andrew T.; Barker, Katherine S.; Rogers, P. David


    Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and in particular, describes the current understanding of molecular basis of azole resistance in these fungal species. PMID:28127295

  2. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial (United States)


    AWARD NUMBER: W81XWH-14-1-0595 TITLE: Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi- Institutional Validation... Institutional Validation Trial 5b. GRANT NUMBER W81XWH-14-1-0595 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Daniel Lin, MD 5d. PROJECT NUMBER 5e. report. Other Products As part of this project we continue to maintain a large biospecimen repository with associated clinical and demographic

  3. Clinical relevance of routinely measured vital signs in hospitalized patients: a systematic review

    NARCIS (Netherlands)

    Storm-Versloot, Marja N.; Verweij, Lotte; Lucas, Cees; Ludikhuize, Jeroen; Goslings, J. Carel; Legemate, Dink A.; Vermeulen, Hester


    Conflicting evidence exists on the effectiveness of routinely measured vital signs on the early detection of increased probability of adverse events. To assess the clinical relevance of routinely measured vital signs in medically and surgically hospitalized patients through a systematic review.

  4. Clinically Relevant Changes in Emotional Expression in Children with ADHD Treated with Lisdexamfetamine Dimesylate (United States)

    Katic, Alain; Ginsberg, Lawrence; Jain, Rakesh; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Scheckner, Brian; Richards, Cynthia; Lasser, Robert; Turgay, Atilla; Findling, Robert L.


    Objective: To describe clinically relevant effects of lisdexamfetamine dimesylate (LDX) on emotional expression (EE) in children with ADHD. Method: Children with ADHD participated in a 7-week, open-label, LDX dose-optimization study. Expression and Emotion Scale for Children (EESC) change scores were analyzed post hoc using two methods to…

  5. Preterm piglets are a clinically relevant model of pediatric GI disease (United States)

    The goal of our research is to establish how nutritional support, enteral versus parenteral, affects gut function and susceptibility to disease in early development. We and others have used the neonatal pig to establish unique models of clinically relevant problems in pediatric gastroenterology, esp...

  6. A Bridge between Two Cultures: Uncovering the Chemistry Concepts Relevant to the Nursing Clinical Practice (United States)

    Brown, Corina E.; Henry, Melissa L. M.; Barbera, Jack; Hyslop, Richard M.


    This study focused on the undergraduate course that covers basic topics in general, organic, and biological (GOB) chemistry at a mid-sized state university in the western United States. The central objective of the research was to identify the main topics of GOB chemistry relevant to the clinical practice of nursing. The collection of data was…

  7. Diagnosing pubovisceral avulsions: a systematic review of the clinical relevance of a prevalent anatomical defect

    NARCIS (Netherlands)

    Lammers, K.; Futterer, J.J.; Prokop, M.; Vierhout, M.E.; Kluivers, K.B.


    The aims of this systematic literature review were to assess whether the detection of pubovisceral avulsions using magnetic resonance (MR) imaging or perineal ultrasonography was clinically relevant in women with pelvic floor dysfunction and to evaluate the relation with anatomy, symptoms, and

  8. Psychometric properties and clinical relevance of the Adolescent Sleep Hygiene Scale in Dutch adolescents

    NARCIS (Netherlands)

    de Bruin, E.J.; van Kampen, R.K.A.; van Kooten, T.; Meijer, A.M.


    Objective: This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. Methods: The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables

  9. Clinical relevancy of nonurinary nitrogen excretion in newborns and infants after digestive tract surgery

    NARCIS (Netherlands)

    Albers, MJIJ; Steyerberg, EW; Tibboel, D


    Background: Whether the contribution of nonurinary nitrogen excretion (N(2)nu) to total nitrogen excretion (N(2)tot) is clinically relevant has not been tested in children in an intensive care unit. Particularly after digestive tract surgery, fecal nitrogen losses, and losses via nasogastric tubes,

  10. Geographical distribution and clinical relevance of non-tuberculous mycobacteria in Croatia

    NARCIS (Netherlands)

    Jankovic, M.; Samarzija, M.; Sabol, I.; Jakopovic, M.; Katalinic Jankovic, V.; Zmak, L.; Ticac, B.; Marusic, A.; Obrovac, M.; Ingen, J. van


    SETTING: The clinical relevance of non-tuberculous mycobacteria (NTM) in Croatia is unknown. OBJECTIVE: To estimate the isolation rate of NTM, record geographical differences and assess the burden of pulmonary NTM disease in Croatia. DESIGN: Nationwide retrospective cohort study of all Croatian

  11. Clinically relevant incidental cardiovascular findings in CT examinations; Klinisch relevante kardiovaskulaere Zufallsbefunde bei CT-Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A. [Universitaetsklinikum Leipzig, Klinik fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Schramm, D.; Bach, A.G. [Universitaetsklinikum Halle (Saale), Klinik fuer Radiologie, Halle (Germany)


    Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [German] Inzidentelle kardiovaskulaere Befunde sind ein haeufiges Phaenomen bei CT-Untersuchungen. Mit dieser Arbeit soll nach gezielter PubMed-Recherche ein systematischer Literaturueberblick ueber die wichtigsten kardiovaskulaeren Zufallsbefunde sowie deren Haeufigkeit und klinische Relevanz gegeben werden. Die Mehrzahl der inzidentellen kardiovaskulaeren Befunde sind klinisch nur von untergeordneter Bedeutung, allerdings werden immer wieder auch hochgradig relevante Zufallsbefunde wie beispielsweise Aortenaneurysmata oder - gerade bei onkologischen Patienten - Thrombosen und thrombembolische Ereignisse detektiert. Jede CT-Untersuchung sollte gezielt nach inzidentellen Befunden durchsucht werden, da diese je nach klinischer Relevanz von entscheidender Bedeutung fuer das weitere klinische Management des Patienten sein koennen. (orig.)

  12. Risks and clinical relevance of medication discrepancies at outpatient departments for mood and anxiety disorders

    NARCIS (Netherlands)

    Simoons, Mirjam; Mulder, Hans; Risselada, Arne J.; Wilmink, Frederik W.; Schoevers, Robert A.; Ruhé, Henricus G.; Van Roon, Eric N.


    OBJECTIVE: To identify discrepancies between actual drug use by outpatients with mood and anxiety disorders and medication overviews from health care providers as well as to investigate the clinical relevance of those discrepancies. DESIGN: Cross-sectional cohort study. METHODS: We included adults

  13. Clinical relevance of and risk factors associated with medication administration time errors

    NARCIS (Netherlands)

    Teunissen, R.; Bos, J.; Pot, H.; Pluim, M.; Kramers, C.


    PURPOSE: The clinical relevance of and risk factors associated with errors related to medication administration time were studied. METHODS: In this explorative study, 66 medication administration rounds were studied on two wards (surgery and neurology) of a hospital. Data on medication errors were

  14. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy

    NARCIS (Netherlands)

    Heetla, Herre W; Staal, Michael; Proost, Johannes H; van Laar, Teus


    Objective: To review all pharmacological and physiological data available on intrathecal baclofen (ITB) therapy and to evaluate its use in clinical practice and future research. Data Sources: PubMed was searched for relevant anatomic, physiological, and pharmacological data available on ITB. Study

  15. There’s an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications

    Directory of Open Access Journals (Sweden)

    Warren Wiechmann, MD, MBA


    Full Text Available Introduction: The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decisionmaking, prescription information and other medical information. The iTunes App Store (Apple, Inc. contains approximately 20,000 apps in its “Medical” category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. Methods: We found applications related to emergency medicine (EM by searching the iTunes App Store for 21 terms representing core content areas of EM, such as “emergency medicine,” “critical care,” “orthopedics,” and “procedures.” Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/ Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. Results: We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store’s “Medical” Category and 0.1% of the overall App Store. Conclusion: Clinically relevant apps represent only a small percentage (6.9% of the total App

  16. Differentiation of Candida albicans, Candida glabrata, and Candida krusei by FT-IR and chemometrics by CHROMagar™ Candida. (United States)

    Wohlmeister, Denise; Vianna, Débora Renz Barreto; Helfer, Virginia Etges; Calil, Luciane Noal; Buffon, Andréia; Fuentefria, Alexandre Meneghello; Corbellini, Valeriano Antonio; Pilger, Diogo André


    Pathogenic Candida species are detected in clinical infections. CHROMagar™ is a phenotypical method used to identify Candida species, although it has limitations, which indicates the need for more sensitive and specific techniques. Infrared Spectroscopy (FT-IR) is an analytical vibrational technique used to identify patterns of metabolic fingerprint of biological matrixes, particularly whole microbial cell systems as Candida sp. in association of classificatory chemometrics algorithms. On the other hand, Soft Independent Modeling by Class Analogy (SIMCA) is one of the typical algorithms still little employed in microbiological classification. This study demonstrates the applicability of the FT-IR-technique by specular reflectance associated with SIMCA to discriminate Candida species isolated from vaginal discharges and grown on CHROMagar™. The differences in spectra of C. albicans, C. glabrata and C. krusei were suitable for use in the discrimination of these species, which was observed by PCA. Then, a SIMCA model was constructed with standard samples of three species and using the spectral region of 1792-1561cm(-1). All samples (n=48) were properly classified based on the chromogenic method using CHROMagar™ Candida. In total, 93.4% (n=45) of the samples were correctly and unambiguously classified (Class I). Two samples of C. albicans were classified correctly, though these could have been C. glabrata (Class II). Also, one C. glabrata sample could have been classified as C. krusei (Class II). Concerning these three samples, one triplicate of each was included in Class II and two in Class I. Therefore, FT-IR associated with SIMCA can be used to identify samples of C. albicans, C. glabrata, and C. krusei grown in CHROMagar™ Candida aiming to improve clinical applications of this technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Candida infanticola and Candida spencermartinsiae yeasts : Possible emerging species in cancer patients

    NARCIS (Netherlands)

    Shokohi, Tahereh; Aslani, Narges; Ahangarkani, Fatemeh; Meyabadi, Masoumeh Fatahi; Hagen, Ferry; Meis, Jacques F.; Boekhout, Teun; Kolecka, Anna; Badali, Hamid


    Opportunistic infections due to Candida species occur frequently especially in intensive care settings. We investigated the prevalence of Candida species among 65 clinical specimens obtained from 200 cancer patients by phenotypic and molecular (ITS sequencing and AFLP) methods. Among the 65 yeast

  18. Candida survival strategies. (United States)

    Polke, Melanie; Hube, Bernhard; Jacobsen, Ilse D


    Only few Candida species, e.g., Candida albicans, Candida glabrata, Candida dubliniensis, and Candida parapsilosis, are successful colonizers of a human host. Under certain circumstances these species can cause infections ranging from superficial to life-threatening disseminated candidiasis. The success of C. albicans, the most prevalent and best studied Candida species, as both commensal and human pathogen depends on its genetic, biochemical, and morphological flexibility which facilitates adaptation to a wide range of host niches. In addition, formation of biofilms provides additional protection from adverse environmental conditions. Furthermore, in many host niches Candida cells coexist with members of the human microbiome. The resulting fungal-bacterial interactions have a major influence on the success of C. albicans as commensal and also influence disease development and outcome. In this chapter, we review the current knowledge of important survival strategies of Candida spp., focusing on fundamental fitness and virulence traits of C. albicans. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. A software system to collect expert relevance ratings of medical record items for specific clinical tasks. (United States)

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K


    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts' ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners.

  20. Facultative Sterol Uptake in an Ergosterol-Deficient Clinical Isolate of Candida glabrata Harboring a Missense Mutation in ERG11 and Exhibiting Cross-Resistance to Azoles and Amphotericin B

    NARCIS (Netherlands)

    Hull, Claire M.; Parker, Josie E.; Bader, Oliver; Weig, Michael; Gross, Uwe; Warrilow, Andrew G. S.; Kelly, Diane E.; Kelly, Steven L.

    We identified a clinical isolate of Candida glabrata (CG156) exhibiting flocculent growth and cross-resistance to fluconazole (FLC), voriconazole (VRC), and amphotericin B (AMB), with MICs of >256, >256, and 32 mu g ml(-1), respectively. Sterol analysis using gas chromatography-mass spectrometry

  1. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. (United States)

    Bailey, D G


    Grapefruit juice interacts with a number of drugs. This commentary provides feedback on a previously proposed approach for predicting clinically relevant interactions with grapefruit juice based on the average inherent oral bioavailability (F) and magnitude of increase in bioavailability with other CYP3A inhibitors of the drug. Additional factors such as variability of the magnitude of the pharmacokinetic interaction among individuals, product monograph cautionary statements and vulnerability of the patient population should be considered. A flow diagram is provided that should improve prediction of the pharmacokinetic interaction and clinical relevance for affected drugs and that recommends different courses of action for patient management. Forecasting the clinical importance of a particular drug interaction with grapefruit can be improved through consideration of additional readily available drug regulatory information. © 2016 John Wiley & Sons Ltd.

  2. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    DEFF Research Database (Denmark)

    Haahtela, T.; Burbach, G. J.; Bachert, C.


    by providing quantitative decision points. MethodsThe GA(2)LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis......, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. ResultsDepending on the allergen, from 40% (blatella......) to 87-89% (grass, mites) of the positive SPT reactions (wheal size3mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive...

  3. Polymicrobial infections involving clinically relevant Gram-negative bacteria and fungi. (United States)

    Dhamgaye, Sanjiveeni; Qu, Yue; Peleg, Anton Y


    Interactions between fungi and bacteria and their relevance to human health and disease have recently attracted increased attention in biomedical fields. Emerging evidence shows that bacteria and fungi can have synergistic or antagonistic interactions, each with important implications for human colonization and disease. It is now appreciated that some of these interactions may be strategic and helps promote the survival of one or both microorganisms within the host. This review will shed light on clinically relevant interactions between fungi and Gram-negative bacteria. Mechanism of interaction, host immune responses, and preventive measures will also be reviewed. © 2016 John Wiley & Sons Ltd.

  4. Music's relevance for children with cancer: music therapists' qualitative clinical data-mining research. (United States)

    O'Callaghan, Clare; Dun, Beth; Baron, Annette; Barry, Philippa


    Music is central in most children's lives. Understanding its relevance will advance efficacious pediatric supportive cancer care. Qualitative clinical data-mining uncovered four music therapists' perspectives about music and music therapy's relevance for pediatric oncology patients up to 14 years old. Inductive and comparative thematic analysis was performed on focus group transcripts and qualitative interrater reliability integrated. Music can offer children a safe haven for internalizing a healthy self-image alongside patient identity. Music therapy can calm, relieve distress, promote supportive relationships, enable self-care, and inspire playful creativity, associated with "normalcy" and hope. Preferred music and music therapy should be available in pediatric oncology.

  5. Candida albicans isolates from a Malaysian hospital exhibit more potent phospholipase and haemolysin activities than non-albicans Candida isolates. (United States)

    Chin, V K; Foong, K J; Maha, A; Rusliza, B; Norhafizah, M; Ng, K P; Chong, P P


    This study was aimed at determining the phospholipase and haemolysin activity of Candida isolates in Malaysia. A total of 37 Candida clinical isolates representing seven species, Candida albicans (12), Candida tropicalis (8), Candida glabrata (4), Candida parapsilosis (1), Candida krusei (4), Candida orthopsilosis (1) and Candida rugosa (7) were tested. In vitro phospholipase activity was determined by using egg yolk plate assay whereas in vitro haemolysin activity was tested by using blood plate assay on sheep blood Sabouraud's dextrose agar (SDA) enriched with glucose. Phospholipase activity was detected in 75% (9 out of 12) of the C. albicans isolates. Among the 25 non- C. albicans Candida isolates, phospholipase activity was detected in only 24% of these isolates. The phospholipase activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.002). Haemolysin activity was detected in 100% of the C. albicans, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. orthopsilosis isolates while 75% of the C. krusei isolates and 12.3% of the C. rugosa isolates showed haemolysin activity. The haemolytic activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.0001).The findings in this study indicate that C. albicans isolates in Malaysia may possess greater virulence potential than the non-albicans species.

  6. Candida infective endocarditis

    NARCIS (Netherlands)

    Baddley, J. W.; Benjamin, D. K.; Patel, M.; Miró, J.; Athan, E.; Barsic, B.; Bouza, E.; Clara, L.; Elliott, T.; Kanafani, Z.; Klein, J.; Lerakis, S.; Levine, D.; Spelman, D.; Rubinstein, E.; Tornos, P.; Morris, A. J.; Pappas, P.; Fowler, V. G.; Chu, V. H.; Cabell, C.; DraGordon, David; Devi, Uma; Spelman, Denis; van der Meer, Jan T. M.; Kauffman, Carol; Bradley, Suzanne; Armstrong, William; Giannitsioti, Efthymia; Giamarellou, Helen; Lerakis, Stamatios; del Rio, Ana; Moreno, Asuncio; Mestres, Carlos A.; Pare, Carlos; Garcia de la Maria, Cristina; de Lazzario, Elisa; Marco, Francesc; Gatell, Jose M.; Miro, Jose M.; Almela, Manel; Azqueta, Manuel; Jimenez-Exposito, Maria Jesus; de Benito, Natividad; Perez, Noel; Almirante, Benito; Fernandez-Hidalgo, Nuria; de Vera, Pablo Rodriguez; Tornos, Pilar; Falco, Vicente; Claramonte, Xavier; Armero, Yolanda; Sidani, Nisreen; Kanj-Sharara, Souha; Kanafani, Zeina; Raglio, Annibale; Goglio, Antonio; Gnecchi, Fabrizio; Suter, Fredy; Valsecchi, Grazia; Rizzi, Marco; Ravasio, Veronica; Hoen, Bruno; Chirouze, Catherine; Leroy, Joel; Plesiat, Patrick; Bernard, Yvette; Casey, Anna; Lambert, Peter; Watkin, Richard; Elliot, Tom; Patel, Mukesh; Dismukes, William; Pan, Angelo; Caros, Giampiero; Tribouilloy, Amel Brahim Mathiron Christophe; Goissen, Thomas; Delahaye, Armelle; Delahaye, Francois; Vandenesch, Francois; Vizzotti, Carla; Nacinovich, Francisco M.; Marin, Marcelo; Trivi, Marcelo; Lombardero, Martin; Cortes, Claudia; Casabe, Jose Horacio; Altclas, Javier; Kogan, Silvia; Clara, Liliana; Sanchez, Marisa; Commerford, Anita; Hansa, Cass; Deetlefs, Eduan; Ntsekhe, Mpiko; Commerford, Patrick; Wray, Dannah; Steed, Lisa L.; Cantey, Robert; Morris, Arthur; Holland, David; Murdoch, David; Graham, Katherine; Read, Kerry; Raymond, Nigel; Bridgman, Paul; Troughton, Richard; Lang, Selwyn; Chambers, Stephen; Kotsanas, Despina; Korman, Tony M.; Peterson, Gail; Purcell, Jon; Southern, Paul M.; Shah, Manisha; Bedimo, Roger; Reddy, Arjun; Levine, Donald; Dhar, Gaurav; Hanlon-Feeney, Alanna; Hannan, Margaret; Kelly, Sinead; Wang, Andrew; Cabell, Christopher; Woods, Christopher; Sexton, Daniel J.; Benjamin, Danny; Corey, G. Ralph; McDonald, Jay R.; Federspiel, Jeff; Engemann, John J.; Barth Reller, L.; Drew, Laura; Caram, L. B.; Stryjewski, Martin; Morpeth, Susan; Lalani, Tahaniyat; Fowler, Vance; Chu, Vivian; Mazaheri, Bahram; Neuerburg, Carl; Naber, Christoph; Athan, Eugene; Henry, Margaret; Harris, Owen; Alestig, Eric; Olaison, Lars; Wikstrom, Lotta; Snygg-Martin, Ulrika; Francis, Johnson; Venugopal, K.; Nair, Lathi; Thomas, Vinod; Chaiworramukkun, Jaruwan; Pachirat, Orathai; Chetchotisakd, Ploenchan; Suwanich, Tewan; Kamarulzaman, Adeeba; Tamin, Syahidah Syed; Premru, Manica Muella; Logar, Mateja; Lejko-Zupanc, Tatjana; Orezzi, Christina; Klein, John; Bouza, Emilio; Moreno, Mar; Rodriguez-Creixems, Marta; Marin, Mercedes; Fernandez, Miguel; Munoz, Patricia; Fernandez, Rocio; Ramallo, Victor; Raoult, Didier; Thuny, Franck; Habib, Gilbert; Casalta, Jean-Paul; Fournier, Pierre-Edouard; Chipigina, Natalia; Kirill, Ozerecky; Vinogradova, Tatiana; Kulichenko, Vadim P.; Butkevich, O. M.; Lion, Christine; Selton-Suty, Christine; Alla, Francois; Coyard, Helene; Doco-Lecompte, Thanh; Larussi, Diana; Durante-Mangoni, Emanuele; Francoise Tripodi, Marie; Utili, Riccardo; Sampath Kumar, A.; Sharma, Gautam; Dickerman, Stuart A.; Street, Alan; Eisen, Damon Peter; McBryde, Emma Sue; Grigg, Leeanne; Abrutyn, Elias; Michelet, Christian; Tattevin, Pierre; Yves Donnio, Pierre; Fortes, Claudio Querido; Edathodu, Jameela; Al-Hegelan, Mashael; Font, Bernat; Raimon Guma, Joan; Cereceda, M.; Oyonarte, Miguel J.; Mella, Rodrigo Montagna; Garcia, Patricia; Braun Jones, Sandra; Isabel de Oliveira Ramos, Auristela; Ley Woon, Lok; Lum, Luh-Nah; Tan, Ru-San; Rees, David; Kornecny, Pam; Lawrence, Richard; Dever, Robyn; Post, Jeffey; Jones, Phillip; Ryan, Suzzane; Harkness, John; Fenely, Michael; Rubinstein, Ethan; Strahilewitz, Jacob; Ionac, Adina; Mornos, Cristian; Dragulescu, Stefan; Forno, Davide; Cecchi, Enrico; de Rosa, Francesco; Imazio, Massimo; Trinchero, Rita; Wiesbauer, Franz; Gattringer, Rainer; Deans, Greg; Andrasevic, Arjana Tambic; Barsic, Bruno; Klinar, Igor; Vincelj, Josip; Bukovski, Suzana; Krajinovic, Vladimir


    Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716

  7. Evaluation of epidemiological cut-off values indicates that biocide resistant subpopulations are uncommon in natural isolates of clinically-relevant microorganisms.

    Directory of Open Access Journals (Sweden)

    Ian Morrissey

    Full Text Available To date there are no clear criteria to determine whether a microbe is susceptible to biocides or not. As a starting point for distinguishing between wild-type and resistant organisms, we set out to determine the minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC distributions for four common biocides; triclosan, benzalkonium chloride, chlorhexidine and sodium hypochlorite for 3319 clinical isolates, with a particular focus on Staphylococcus aureus (N = 1635 and Salmonella spp. (N = 901 but also including Escherichia coli (N = 368, Candida albicans (N = 200, Klebsiella pneumoniae (N = 60, Enterobacter spp. (N = 54, Enterococcus faecium (N = 53, and Enterococcus faecalis (N = 56. From these data epidemiological cut-off values (ECOFFs are proposed. As would be expected, MBCs were higher than MICs for all biocides. In most cases both values followed a normal distribution. Bimodal distributions, indicating the existence of biocide resistant subpopulations were observed for Enterobacter chlorhexidine susceptibility (both MICs and MBCs and the susceptibility to triclosan of Enterobacter (MBC, E. coli (MBC and MIC and S. aureus (MBC and MIC. There is a concern on the potential selection of antibiotic resistance by biocides. Our results indicate however that resistance to biocides and, hence any potential association with antibiotic resistance, is uncommon in natural populations of clinically relevant microorganisms.

  8. [Antifungal susceptibility profiles of Candida species to triazole: application of new CLSI species-specific clinical breakpoints and epidemiological cutoff values for characterization of antifungal resistance]. (United States)

    Karabıçak, Nilgün; Alem, Nihal


    The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antifungal Susceptibility Testing has newly introduced species-specific clinical breakpoints (CBPs) for fluconazole and voriconazole. When CBPs can not be determined, wild-type minimal inhibitory concentration (MIC) distributions are detected and epidemiological cutoff values (ECVs) provide valuable means for the detection of emerging resistance. The aim of this study is to determine triazole resistance patterns in Candida species by the recently revised CLSI CBPs. A total of 140 Candida strains isolated from blood cultures of patients with invasive candidiasis hospitalized in various intensive care units in Turkey and sent to our reference laboratory between 2011-2012, were included in the study. The isolates were identified by conventional methods, and susceptibility testing was performed against fluconazole, itraconazole and voriconazole, by the 24-h CLSI broth microdilution (BMD) method. Azole resistance rates for all Candida species were determined using the new species-specific CLSI CBPs and ECVs criteria, when appropriate. The species distribution of the isolates were as follows; C.parapsilosis (n= 31 ), C.tropicalis (n= 26 ), C.glabrata (n= 21), C.albicans (n= 18), C.lusitaniae (n= 16), C.krusei (n= 16), C.kefyr (n= 9), C.guilliermondii (n= 2), and C.dubliniensis (n= 1). According to the newly determined CLSI CBPs for fluconazole and C.albicans, C.parapsilosis, C.tropicalis [susceptible (S), ≤ 2 µg/ml; dose-dependent susceptible (SDD), 4 µg/ml; resistant (R), ≥ 8 µg/ml], and C.glabrata (SDD, ≤ 32 µg/ml; R≥ 64 µg/ml) and for voriconazole and C.albicans, C.parapsilosis, C.tropicalis (S, ≤ 0.12 µg/ml; SDD, 0.25-0.5 µg/ml; R, ≥ 1 µg/ml), and C.krusei (S, ≤ 0.5 µg/ml; SDD, 1 µg/ml; R, ≥ 2 µg/ml), it was found that three of C.albicans, one of C.parapsilosis and one of C.glabrata isolates were resistant to fluconazole, while two of C.albicans and two of C

  9. Online drug databases: a new method to assess and compare inclusion of clinically relevant information. (United States)

    Silva, Cristina; Fresco, Paula; Monteiro, Joaquim; Rama, Ana Cristina Ribeiro


    Evidence-Based Practice requires health care decisions to be based on the best available evidence. The model "Information Mastery" proposes that clinicians should use sources of information that have previously evaluated relevance and validity, provided at the point of care. Drug databases (DB) allow easy and fast access to information and have the benefit of more frequent content updates. Relevant information, in the context of drug therapy, is that which supports safe and effective use of medicines. Accordingly, the European Guideline on the Summary of Product Characteristics (EG-SmPC) was used as a standard to evaluate the inclusion of relevant information contents in DB. To develop and test a method to evaluate relevancy of DB contents, by assessing the inclusion of information items deemed relevant for effective and safe drug use. Hierarchical organisation and selection of the principles defined in the EGSmPC; definition of criteria to assess inclusion of selected information items; creation of a categorisation and quantification system that allows score calculation; calculation of relative differences (RD) of scores for comparison with an "ideal" database, defined as the one that achieves the best quantification possible for each of the information items; pilot test on a sample of 9 drug databases, using 10 drugs frequently associated in literature with morbidity-mortality and also being widely consumed in Portugal. Main outcome measure Calculate individual and global scores for clinically relevant information items of drug monographs in databases, using the categorisation and quantification system created. A--Method development: selection of sections, subsections, relevant information items and corresponding requisites; system to categorise and quantify their inclusion; score and RD calculation procedure. B--Pilot test: calculated scores for the 9 databases; globally, all databases evaluated significantly differed from the "ideal" database; some DB performed

  10. Interference of cationic polymeric nanoparticles with clinical chemistry tests--clinical relevance. (United States)

    Shcharbin, Dzmitry; Shcharbina, Natallia; Milowska, Katarzyna; de la Mata, Francisco Javier; Muñoz-Fernandez, Maria Angeles; Mignani, Serge; Gomez-Ramirez, Rafael; Majoral, Jean-Pierre; Bryszewska, Maria


    The development of medical nanosystems requires knowledge of their behavior in vivo. Clinical chemistry tests are widely used to estimate the systemic toxicity of nanoparticles. In this paper we have explored the impact of small positively charged nanoparticles-poly(amidoamine), phosphorous and carbosilane dendrimers - on biochemical parameters of standardized serum in vitro. All the dendrimers could shift the main biochemical parameters. Thus, in the case of patients having the normal, but 'boundary', values of biochemical parameters, nanoparticle-induced changes can be wrongly interpreted as evidence of some dysfunctions (hepatic, renal, etc.). Moreover, the effects of nanoparticles of metals, carbon nanotubes, quantum dots, fullerenes, dendrimers having been sized up to 4000 nm and the hundreds of reactive groups, can be significantly higher. Thus, preliminary evaluation of any nanomaterial in vitro is required in clinical chemistry tests before its application in vivo to draw the correct conclusions and benefit animals. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. European Good Laboratory and Clinical Practices: their relevance to clinical pathology laboratories. (United States)

    Dent, N J


    The requirements for Good Laboratory (GLP) and Good Clinical Practices (CGP) were established as a matter of urgency by the United States in the early 1970s. These were in response to gross misconduct and, in many instances, fraud. Over the next 15 years, a plethora of regulatory principles, guidelines, and regulations was produced by many countries of the world, culminating in single standards for European, Japanese, and United States authorities. Although with regard to GLP this has basically become a worldwide recognized standard within the preclinical (toxicology) studies, in the veterinary, chemical, agrochemical, and pharmaceutical industries, the GCPs are now seeing a rebirth. Within a clinical trials environment, there is most certainly a requirement for compliance with GCP, especially with regard to the harmonization of data within the European Community. The goal of this article is to cover the following aspects: Why should we have good practices? Why should laboratory data be audited? Why is there a need for a QA unit or function? What is the QA operational approach? How does a laboratory audit take place within laboratories? In discussing the laboratories and their subsequent data audits, the pitfalls and benefits are addressed and an examination of the data from the sponsor's viewpoint is compared with that produced by the laboratory. The types of laboratories present in a clinical environment are examined. They obviously comprise clinical pathology, microbiology, and analytical as well as ancillary hospital areas such as X-ray and cardiology. These laboratories may also be in the private sector, the National Health Service, contract laboratories, universities, or the general practitioner population.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. A head and neck lymph node classification using an anatomical grid system while maintaining clinical relevance. (United States)

    Benninger, Brion; Barrett, Richard


    The current classification of head and neck lymph nodes lacks a standardized system that integrates basic anatomy and clinical relevance. Currently, anatomy texts, atlases, and journals used to educate future health care professionals use a classification system that differs from the commonly used clinical nomenclature. As a result, student trainees entering the professional world are confused by lymph node terminology. The purpose of this study was to suggest a lymph node classification system that accurately reflected anatomy and clinical applications. A literature search was conducted on anatomic and clinical texts, atlases, journals, and Web sites. Two recurring classification themes were found from anatomic texts and atlases: superficial and deep chains, and local anatomic structures. Since 1988 the clinical specialties have used a Roman numeral "level" system. The differences between anatomic and clinical classification systems have led to academic frustration. After analysis, a functional classification system was developed that integrated anatomic and clinical terminology from the current classification systems. This suggested system revised the clinically accepted level system approved in 1988 and replaced the terminology with an anatomically derived naming system. This system satisfies the need for a classification that unifies anatomic and clinical applications. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Establishing a clinically relevant cutoff to the Dependency Scale from the dimensional clinical personality inventory. (United States)

    Carvalho, Lucas de F; Pianowski, Giselle; Filho, Nelson H


    The Clinical Dimensional Personality Inventory (IDCP) is a 163-item self-report tool developed for the assessment of 12 dimensions of personality pathology. One of the scales comprising the instrument-the Dependency scale-is intended to provide psychometric information on traits closely related to the Dependent Personality Disorder (DPD). In the present study, we used both Item Response Theory modeling and Receiver Operating Characteristic curve analysis to establishing a clinically meaningful cutoff for the IDCP Dependency Scale. Participants were 2.481 adults, comprised by outpatients diagnosed with DPD, outpatients diagnosed with other PDs, and adults from the general population. The Wright's item map graphing technique revealed that outpatients were located at the very high levels in the latent scale continuum of the Dependency Scale, with a very large effect size for the mean difference between patients and non-patients. The ROC curve analysis supported a cutoff at 2.3 points in the Dependency Scale, which yielded 0.86 of sensitivity and 0.79 of specificity. Findings from the present investigation suggest the IDCP Dependency Scale is useful as a screening tool of the core features of the DPD. We address potential clinical applications for the instrument, and discuss limitations from the present study. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor


    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal...... and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft...... enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat...

  15. Clinical Relevance of Cement Leakage after Radiofrequency Kyphoplasty vs. Balloon Kyphoplasty: A Prospective Randomised Study. (United States)

    Riesner, H-J; Kiupel, K; Lang, P; Stuby, F; Friemert, B; Palm, H-G


    Cement leakage is regarded as a typical complication of cement-based augmentation of vertebral fractures. The gold standard is balloon kyphoplasty (BK). Recent methods, such as radiofrequency kyphoplasty (RFK), must be compared with BK in terms of therapeutic success and complication rates. It is unclear whether the cement leakage rate in RFK is lower than with BK and whether this has any clinical relevance. Therefore, the aim of our prospective clinical study was to compare RFK with BK with respect to cement leakage rates and associated clinical complications. After prospective randomisation, 100 patients (76 women and 24 men with an average age of 78.5 years) or 162 vertebral bodies were treated by BK (n = 79) or RFK (n = 83). We evaluated the parameters "localisation of cement leakage" (epidural, intradiscal, extracorporal, intravascular) and "clinical relevance". More cement is used in BK (5.2 ml) than in RFK (4.0 ml, p = 0.001). Cement leakage was found in 48/79 patients (60.8 %) with BK and 53/83 patients (63.9 %) with RFK (p = 0.420). Even subanalysis by location showed no significant difference between the two methods. Despite the high leakage rates, we experienced only two cases (1× BK, 1× RFK) with intravascular leakage in the inferior vena cava, with interventional endovascular salvage. The two examined kyphoplasty methods (BK vs. RFK) have the same high rates of cement leakage, but are rarely associated with clinically manifest complications. Clinically relevant differences between the two compared kyphoplasty methods could not be found. Georg Thieme Verlag KG Stuttgart · New York.

  16. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  17. Taijin Kyofusho and Social Anxiety and Their Clinical Relevance in Indonesia and Switzerland (United States)

    Vriends, N.; Pfaltz, M. C.; Novianti, P.; Hadiyono, J.


    Background: Taijin Kyofusho Scale (TKS) is an interpersonal fear to offend others and is defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a culturally bound syndrome that occurs in Japan and Korea. Recently, cases with TKS have also been recognized in other cultures. The present questionnaire study investigated self-report TKS symptoms and social anxiety symptoms, and their clinical relevance in an Indonesian and Swiss sample. It also investigated whether self-construal is associated with TKS and social anxiety, and if self-construal is a mediator of the expected association between cultural background and social anxiety and TKS symptoms. Method: 311 Indonesian and 349 Swiss university students filled out the Liebowitz Social Anxiety Scale, the Taijin Kyofusho Scale, the Self-Construal Scale, self-report social phobia DSM-IV criteria, and rated their wish for professional help to deal with social fears. Results: TKS and social anxiety symptoms were higher in the Indonesian than the Swiss sample. TKS symptoms were associated with clinical relevance in Indonesia, whereas in Switzerland only social anxiety symptoms were associated with clinical relevance. Independent self-construal was negatively associated and interdependent self-construal was positively associated with TKS and social anxiety symptoms. Interdependent self-construal mediated the association between cultural background and these symptoms. Discussion: TKS might be a clinically relevant syndrome in all individuals or cultures with an interdependent self-construal or less independent self-construal. The proposal to include the fear of offending others in the DSM-V criteria of social phobia is supported by the present findings. PMID:23382720

  18. Targeted testing with diethylthiourea often reveals clinically relevant allergic contact dermatitis caused by neoprene rubber

    DEFF Research Database (Denmark)

    Dall, Anne B-H; Andersen, Klaus Ejner; Mortz, Charlotte G


    Background. Diethylthiourea is widely used in the rubber industry, particularly in neoprene rubber, and may cause allergic contact dermatitis. However, as thiourea allergens are not part of the European baseline series, the diagnosis of allergic contact dermatitis caused by thiourea compounds......, and positive reactions were found in 15% (13/88). Thus, 15% (37/239) had positive patch test reactions to diethylthiourea, all with current clinical relevance and all strong. Conclusion. Clinical suspicion of neoprene rubber allergy and subsequent aimed patch testing with diethylthiourea give a high yield...

  19. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys


    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  20. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Banys, Malgorzata, E-mail: [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany); Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg D-22087 (Germany); Krawczyk, Natalia; Fehm, Tanja [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany)


    Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs) in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  1. Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors. (United States)

    Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K


    Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

  2. Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation. (United States)

    Ravichandran, Akhilandeshwari; Liu, Yuchun; Teoh, Swee-Hin


    In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non-invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non-invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the 'push' of bioreactor systems into the commercial market as well as 'pull' factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Using mixed methods to identify and answer clinically relevant research questions. (United States)

    Shneerson, Catherine L; Gale, Nicola K


    The need for mixed methods research in answering health care questions is becoming increasingly recognized because of the complexity of factors that affect health outcomes. In this article, we argue for the value of using a qualitatively driven mixed method approach for identifying and answering clinically relevant research questions. This argument is illustrated by findings from a study on the self-management practices of cancer survivors and the exploration of one particular clinically relevant finding about higher uptake of self-management in cancer survivors who had received chemotherapy treatment compared with those who have not. A cross-sectional study generated findings that formed the basis for the qualitative study, by informing the purposive sampling strategy and generating new qualitative research questions. Using a quantitative research component to supplement a qualitative study can enhance the generalizability and clinical relevance of the findings and produce detailed, contextualized, and rich answers to research questions that would be unachievable through quantitative or qualitative methods alone. © The Author(s) 2015.

  4. Status of Removable Dentures and Relationship with Oral Candida-Associated Factors in a Geriatric Population in Catalonia. (United States)

    Martori, Elisenda; Ayuso-Montero, Raúl; Willaert, Eva; Viñas, Miguel; Peraire, Maria; Martinez-Gomis, Jordi


    Colonization by Candida is related to wearing a denture. How denture type, status, and maintenance play a role in determining Candida colonization remains unknown. This work evaluated removable denture status in an elderly population and explored the association between denture-related factors and oral Candida colonization as determined by systemic and local factors. Socio-demographic, general health, and behavioral data and oral factors were registered by means of a questionnaire. Oral, dental, and denture-related factors were assessed by clinical examination, and yeasts were isolated from oral and denture specimens. Multiple logistic regression analysis was used to explore the relative relevance of risk factors. Overall, 52.4% of subjects used complete dentures in both lower and upper arches, and 90% of the prostheses were in good condition. Denture plaque index was high in most cases, and 75% of subjects had yeasts in their oral cavities. Oral Candida colonization was significantly associated with low saliva pH, sugar consumption, and the fault of a denture component; however, only sugar consumption was found to be an independent factor related with oral Candida colonization, showing an odds ratio of 3.04 in a multiple logistic regression model. Elderly people in this study used a complete denture in good condition, with a median age of 15 years. Daily or weekly sugar consumption was found to be highly associated with oral colonization by Candida. © 2016 by the American College of Prosthodontists.

  5. Overexpression of aldo-keto-reductase in azole-resistant clinical isolates of Candida glabrata determined by cDNA-AFLP

    Directory of Open Access Journals (Sweden)

    Farahyar Shirin


    Full Text Available Abstract Background Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata. Methods The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection in immunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazole and itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns of the organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI. The potential gene(s implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP. Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s in resistant isolates as compared to sensitive and reference strains. Results and conclusions The aldo-keto-reductase superfamily (AKR gene was upregulated in the resistant clinical isolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.

  6. Multi-species biofilm of Candida albicans and non-Candida albicans Candida species on acrylic substrate

    Directory of Open Access Journals (Sweden)

    Apurva K Pathak


    Full Text Available OBJECTIVE: In polymicrobial biofilms bacteria extensively interact with Candida species, but the interaction among the different species of the Candida is yet to be completely evaluated. In the present study, the difference in biofilm formation ability of clinical isolates of four species of Candida in both single-species and multi-species combinations on the surface of dental acrylic resin strips was evaluated. MATERIAL AND METHODS: The species of Candida, isolated from multiple species oral candidiasis of the neutropenic patients, were used for the experiment. Organisms were cultured on Sabouraud dextrose broth with 8% glucose (SDB. Biofilm production on the acrylic resins strips was determined by crystal violet assay. Student's t-test and ANOVA were used to compare in vitro biofilm formation for the individual species of Candida and its different multi-species combinations. RESULTS: In the present study, differences between the mean values of the biofilm-forming ability of individual species (C. glabrata>C. krusei>C. tropicalis>C. albicans and in its multi-species' combinations (the highest for C. albicans with C. glabrata and the lowest for all the four species combination were reported. CONCLUSIONS: The findings of this study showed that biofilm-forming ability was found greater for non-Candida albicans Candida species (NCAC than for C. albicans species with intra-species variation. Presence of C. albicans in multi-species biofilms increased, whereas; C. tropicalis decreased the biofilm production with all other NCAC species.

  7. Developing students' clinical reasoning skills: correlates of perceived relevance of two teaching and learning approaches. (United States)

    Postma, T C; White, J G


    'Relevance' is a key concept in adult learning. Hence, this study sought to examine students' perceptions of relevance of the teaching and learning in relation to different instructional designs employed in a Comprehensive Patient Care (CPC) course that aims to develop integrated clinical reasoning skills. Third to fifth year students (2009-2011) were asked to anonymously rate the relevance of the instructional design (RELID) they participated in by means of visual analogue scales at the School of Dentistry, University of Pretoria. They were also asked to rate their perceptions of the alignment between teaching and learning and outcomes (ATLO), assessments' contribution to learning (ACL), course organisation (CO) and teacher competence (TC). RELID served as the outcome measure in stepwise linear regression analyses. ATLO, ACL, CO, TC and the instructional design (case-based learning (CBL = 1) and the combination of discipline-based and lecture-based teaching in CPC (DB-LBT = 0)) served as the co-variables for each of the years of study. The analyses showed positive correlations between RELID and ATLO and between RELID and ACL for all the years of study. RELID was associated with TC in year three and four and CO was associated with RELID in year four and five. CBL outperformed DB-LBT in terms of perceived relevance of the teaching and learning. The results suggest that students' perceptions of the relevance of the instructional design may be enhanced when outcomes, teaching, learning and assessment are constructively aligned during the development of clinical reasoning skills. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Rachinger Andrea


    Full Text Available Abstract Background In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas. Methods We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750 in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1 were quantified in 62 cancer tissues by real-time RT-PCR. Results Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy. Conclusion In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.

  9. Clinical relevance of comorbidity in anxiety disorders: A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Klein Hofmeijer-Sevink, M.; Batelaan, N.M.; van Megen, H.J.G.M.; Penninx, B.W.J.H.; Cath, D.C.; van Hout, M.A.; van Balkom, A.J.L.M.


    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  10. Clinical relevance of comorbidity in anxiety disorders : A report from the Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Hofmeijer-Sevink, Mieke Klein; Batelaan, Neeltje M.; van Megen, Harold J. G. M.; Penninx, Brenda W.; Cath, Danielle C.; van den Hout, Marcel A.; van Balkom, Anton J. L. M.

    Background: To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive

  11. Synergistic in vitro activity of sodium houttuyfonate with fluconazole against clinical Candida albicans strains under planktonic growing conditions. (United States)

    Shao, Jing; Cui, YanYan; Zhang, MengXiang; Wang, TianMing; Wu, DaQiang; Wang, ChangZhong


    Fluconazole resistance is an intractable problem of treating Candida albicans, calling for more antifungal agents to enhance the activity of fluconazole. This work investigates the anti-C. albicans activities of sodium houttuyfonate (SH) and/or fluconazole and the associated mechanism. The minimum inhibitory concentrations (MICs) of SH and fluconazole both ranging from 0.5 to 1024 μg/mL were determined by broth microdilution method in 19 C. albicans isolates, and their fractional inhibitory concentration index (FICI) was evaluated by checkerboard assay. After MICSH and/or MICfluconazole treatments, the expressions of IFD6, PHR1, ZAP1, ADH5, BGL2, XOG1 and FKS1 were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans 1601. The MICs of SH alone ranged from 32 to 256 μg/mL and decreased 2-16-fold in combination. SH showed strong synergism with fluconazole with FICI fluconazole slightly inhibited the expression of IFD6 and PHR1 by 1.23- and 1.35-fold (p > 0.05), but promoted evidently the expression of ZAP1, ADH5, XOG1 and FKS1 by 1.98-, 3.56-, 4.10- and 2.86-fold (p fluconazole in C. albicans resistant isolates, and the underlying mechanism may be associated with β-1,3-glucan synthesis and transportation.

  12. Overexpression of Aldo-Keto-Reductase in Azole-resistant Clinical Isolates of Candida Glabrata Determined by cDNA-AFLP

    Directory of Open Access Journals (Sweden)

    Mansour Heidari


    Full Text Available Background: Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata.Methods: The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection inimmunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazoleand itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns ofthe organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI. The potentialgene(s implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP. Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s in resistant isolates as compared to sensitive and reference strains.Results and conclusions: The aldo-keto-reductase superfamily (AKR gene was upregulated in the resistant clinicalisolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.

  13. Phytochemicals as Inhibitors of Candida Biofilm. (United States)

    Raut, Jayant Shankar; Karuppayil, Sankunny Mohan


    Candida biofilm and associated infections is a serious threat to the large population of immunocompromised patients. Biofilm growth on prosthetic devices or host tissue shows reduced sensitivity to antifungal agents and persists as a reservoir of infective cells. Options for successful treatment of biofilm associated Candida infections are restricted because most of the available antifungal drugs fail to eradicate biofilms. Various plant actives are known to possess interesting antifungal properties. To explore and review the potential of phytochemicals as a novel strategy against Candida biofilms is the intent of present article. Thorough literature search is performed to identify Candida biofilm inhibitors of plant origin. An account of efficacy of selected phytochemicals is presented taking into consideration their biofilm inhibitory concentrations. This review discusses biofilm formation by Candida species, their involvement in human infections, and associated drug resistance. It gives insight into the biofilm inhibitory potential of various phytochemicals. Based on the available reports including the work done in our laboratory, several plant extracts, essential oils and phytomolecules have been identified as excellent inhibitors of biofilms of C. albicans and non-albicans Candida species (NACS). Selected phytochemicals which exhibit activities at low concentrations without displaying toxicity to host are potential therapeutic agents against biofilm associated Candida infections. In vivo testing in animal models and clinical trials in humans are required to be taken up seriously to propose few of the phytochemicals as candidate drug molecules.

  14. Comparison of the Vitek 2 yeast susceptibility system with CLSI microdilution for antifungal susceptibility testing of fluconazole and voriconazole against Candida spp., using new clinical breakpoints and epidemiological cutoff values. (United States)

    Pfaller, Michael A; Diekema, Daniel J; Procop, Gary W; Rinaldi, Michael G


    A commercially available, fully automated yeast susceptibility test system (Vitek 2; bioMérieux, Marcy d'Etoile, France) was compared in 3 different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference microdilution (BMD) method by testing 2 quality control strains, 10 reproducibility strains, and 425 isolates of Candida spp. against fluconazole and voriconazole. Reference CLSI BMD MIC endpoints and Vitek 2 MIC endpoints were read after 24 hours and 9.1-27.1 hours incubation, respectively. Excellent essential agreement (within 2 dilutions) between the reference and Vitek 2 MICs was observed for fluconazole (97.9%) and voriconazole (96.7%). Categorical agreement (CA) between the 2 methods was assessed using the new species-specific clinical breakpoints (CBPs): susceptible (S) ≤2 μg/mL, susceptible dose-dependent (SDD) 4 μg/mL, and resistant (R) ≥8 μg/mL for fluconazole and Candida albicans, Candida tropicalis, and Candida parapsilosis and ≤32 μg/mL (SDD), ≥64 μg/mL (R) for Candida glabrata; S ≤0.12 μg/mL, SDD 0.25-0.5 μg/mL, R ≥1 μg/mL for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis, and ≤0.5 μg/mL (S), 1 μg/mL (SDD), ≥2 μg/mL (R) for Candida krusei. The epidemiological cutoff value (ECV) of 0.5 μg/mL for voriconazole and C. glabrata was used to differentiate wild-type (WT; MIC ≤ ECV) from non-WT (MIC > ECV) strains of this species. Due to the lack of CBPs for the less common species, the ECVs for fluconazole and voriconazole, respectively, were used for Candida lusitaniae (2 μg/mL and 0.03 μg/mL), Candida dubliniensis (0.5 μg/mL and 0.03 μg/mL), Candida guilliermondii (8 μg/mL and 0.25 μg/mL), and Candida pelliculosa (4 μg/mL and 0.25 μg/mL) to categorize isolates of these species as WT and non-WT. CA between the 2 methods was 96.8% for fluconazole and 96.5% for voriconazole with less than 1% very major errors and 1.3-3.0% major errors. The Vitek 2 yeast susceptibility system

  15. Current strategies and findings in clinically relevant post-translational modification-specific proteomics. (United States)

    Pagel, Oliver; Loroch, Stefan; Sickmann, Albert; Zahedi, René P


    Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

  16. Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework (United States)

    Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin


    Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

  17. Development of Candida-associated denture stomatitis: new insights

    Directory of Open Access Journals (Sweden)

    Tatiana Pereira-Cenci


    Full Text Available Despite therapeutic progress, opportunistic oral fungal infectious diseases have increased in prevalence, especially in denture wearers. The combination of entrapment of yeast cells in irregularities in denture-base and denture-relining materials, poor oral hygiene and several systemic factors is the most probable cause for the onset of this infectious disease. Hence colonization and growth on prostheses by Candida species are of clinical importance. The purpose of this review is to critically discuss several key factors controlling the adhesion of Candida species which are relevant to denture-associated stomatitis. Although there is some consensus on the role of surface properties, studies on several other factors, as the use of denture liners, salivary properties and yeast-bacterial interactions, have shown contradictory findings. A comprehensive fundamental understanding is hampered by conflicting findings due to the large variations in experimental protocols, while other factors have never been thoroughly studied. Surface free energy and surface roughness control the initial adherence, but temporal changes have not been reported. Neither have in vivo studies shown if the substratum type is critical in dictating biofilm accumulation during longer periods in the oral environment. The contribution of saliva is unclear due to factors like variations in its collection and handling. Initial findings have disclosed that also bacteria are crucial for the successful establishment of Candida in biofilms, but the clinical significance of this observation is yet to be confirmed. In conclusion, there is a need to standardize experimental procedures, to bridge the gap between laboratory and in vivo methodologies and findings and - in general - to thoroughly investigate the factors that modulate the initial attachment and subsequent colonization of denture-base materials and the oral mucosa of patients subjected to Candida infections. Information on how

  18. Balancing Clinical and Pathologic Relevence in the Machine Learning Diagnosis of Epilepsy. (United States)

    Kerr, Wesley T; Cho, Andrew Y; Anderson, Ariana; Douglas, Pamela K; Lau, Edward P; Hwang, Eric S; Raman, Kaavya R; Trefler, Aaron; Cohen, Mark S; Nguyen, Stefan T; Reddy, Navya M; Silverman, Daniel H


    The application of machine learning to epilepsy can be used both to develop clinically useful computer-aided diagnostic tools, and to reveal pathologically relevant insights into the disease. Such studies most frequently use neurologically normal patients as the control group to maximize the pathologic insight yielded from the model. This practice yields potentially inflated accuracy because the groups are quite dissimilar. A few manuscripts, however, opt to mimic the clinical comparison of epilepsy to non-epileptic seizures, an approach we believe to be more clinically realistic. In this manuscript, we describe the relative merits of each control group. We demonstrate that in our clinical quality FDG-PET database the performance achieved was similar using each control group. Based on these results, we find that the choice of control group likely does not hinder the reported performance. We argue that clinically applicable computer-aided diagnostic tools for epilepsy must directly address the clinical challenge of distinguishing patients with epilepsy from those with non-epileptic seizures.

  19. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment. (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D


    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  20. In vitro activities of voriconazole as a triazole derivative and caspofungin as an echinocandin were compared with those of some antifungal agents against Candida species isolated from clinical specimens. (United States)

    Ozçelik, Berrin; Kaynak, Fatma; Cesur, Salih; Sipahi, Bilge; Sultan, Nedim


    We evaluated the in vitro activity of ketoconazole (KET), fluconazole (FLU), amphotericin B (AmpB), and flucytosine (FCU) in comparison to voriconazole (VOR) as a triazole derivative and caspofungin (CAS) as an echinocandin against 114 Candida spp. isolated from different cultures (blood, urine, sputum). The most common species of identified Candida were C. albicans (88), followed by C. parapsilosis (8), C. glabrata (7), C. tropicalis (6), C. famata (2), C. kefyr (2), and C. sake (1). The Clinical and Laboratory Standards Institute M 27-A method was used to evaluate the activity of antifungal agents. The minimal inhibitory concentrations of the strains were evaluated by RPMI 1640 medium using a microdilution method. Of 114 isolates, 100% were sensitive to AmpB, VOR, and CAS, 1.75% showed intermediate resistant to FCU also 0.87% showed intermediate resistant to FLU, and 2.63% were fully resistant to FLU and FCU. These results suggest that KET, AmpB, CAS, and VOR demonstrated excellent activity against all Candida spp. Taken together; these antifungal agents should be effective in the treatment of a broad range of Candida infections.

  1. Impulsivity is relevant for trauma exposure and PTSD symptoms in a non-clinical population. (United States)

    Netto, Liana R; Pereira, Juliana L; Nogueira, José F; Cavalcanti-Ribeiro, Patrícia; Santana, Rejane Conceição; Teles, Carlos A; Koenen, Karestan C; Quarantini, Lucas C


    Impulsivity is a relevant construct for explaining both normal individual differences in personality and more extreme personality disorder, and is often investigated within clinical populations. This study aims to explore the college students' impulsivity patterns and to investigate the association across levels of impulsivity with trauma exposure and PTSD development in a non-clinical population. A one-phase census survey of seven college institutions assessed 2213 students in three metropolitan regions of Northeastern Brazil. All subjects anonymously completed a self-applied protocol consisting of: a socio-demographic questionnaire, Trauma History Questionnaire (THQ), PTSD Checklist (PCL-C), and Barratt Impulsiveness Scale (BIS-11). The median for frequency of trauma exposure was 4 events for people with low and normal impulsivity, and 6 for highly impulsive ones. Individuals with higher impulsivity presented earlier exposition than non-impulsive ones, and worst outcome: 12.4% with PTSD, against 8.4% and 2.3% (normal and low impulsivity). Of the three factors of impulsivity, the Attentional factor conferred the strongest association with PTSD development. Results suggest that impulsivity is also a relevant trait in a non-clinical population and is associated with trauma exposure and PTSD. Strategies to promote mental health in adolescents may be pertinent, especially with the aim of managing impulsivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms. (United States)

    Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan


    This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

  3. Fear of cancer recurrence: a theoretical review and its relevance for clinical presentation and management. (United States)

    Simonelli, Laura E; Siegel, Scott D; Duffy, Nicole M


    There is increasing recognition of the unique physical and psychosocial concerns of the growing population of cancer survivors. An emerging literature demonstrates that fear of cancer recurrence (FCR) is a problematic long-term and late effect for cancer survivors. In fact, FCR is a top concern, and this article provides a necessary synthesis of the extant research evidence and theory. Literature searches were conducted using databases including MEDLINE and PsychINFO using specified search terms including 'fear of recurrence' and 'worry about recurrence'. A comprehensive narrative review summarizes early empirical findings on FCR including current definitions, assessment tools, clinical presentations, quality of life impact, prevalence, trajectory and risk factors. This paper also critically reviews the relevant theoretical frameworks to best understand these findings and considers multiple psychosocial treatment models that may have relevance for addressing FCR in the clinical setting. There is evidence of substantial prevalence and quality of life impact of FCR. Several theories (e.g. self-regulation model of illness, a family-based model, uncertainty in illness theory, social-cognitive processing theory, terror management theory) directly or indirectly help conceptualize FCR and inform potential treatment options for those with clinically significant distress or impairment resulting from FCR. Further investigation into FCR is warranted to promote evidence-based care for this significant cancer survivorship concern. Copyright © 2016 John Wiley & Sons, Ltd.

  4. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre


    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  5. Found in Translation: Maximizing the Clinical Relevance of Nonclinical Oncology Studies. (United States)

    Spilker, Mary E; Chen, Xiaoying; Visswanathan, Ravi; Vage, Chandra; Yamazaki, Shinji; Li, Gang; Lucas, Judy; Bradshaw-Pierce, Erica L; Vicini, Paolo


    Purpose: The translation of nonclinical oncology studies is a subject of continuous debate. We propose that translational oncology studies need to optimize both pharmacokinetic (drug exposure) and pharmacodynamic (xenograft model) aspects. While improvements in pharmacodynamic translatability can be obtained by choosing cell lines or patient-derived xenograft models closer to the clinical indication, significant ambiguity and variability exists when optimizing the pharmacokinetic translation of small molecule and biotherapeutic agents. Experimental Design and Results: In this work, we propose a pharmacokinetic-based strategy to select nonclinical doses for approved drug molecules. We define a clinically relevant dose (CRD) as the dosing regimen in mice that most closely approximates the relevant pharmacokinetic metric in humans. Such metrics include area under the time-concentration curve and maximal or minimal concentrations within the dosing interval. The methodology is applied to six drugs, including targeted agents and chemotherapeutics, small and large molecules (erlotinib, dasatinib, vismodegib, trastuzumab, irinotecan, and capecitabine). The resulting efficacy response at the CRD is compared with clinical responses. Conclusions: We conclude that nonclinical studies designed with the appropriate CRDs of approved drug molecules will maximize the translatability of efficacy results, which is critical when testing approved and investigational agents in combination. Clin Cancer Res; 23(4); 1080-90. ©2016 AACR . ©2016 American Association for Cancer Research.

  6. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature. (United States)

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P


    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.

  7. Continuous urethral pressure measurements; measurement techniques; pressure variations; clinical interpretations; and clinical relevance. A Systematic Literature Analysis. (United States)

    Kummeling, Maxime T M; Rosier, Peter F W M; Elzevier, Henk W; Groenendijk, Pieter M


    The clinical relevance of urethral pressure variations (UPV) in the pathophysiology of over active bladder syndrome (OAB) has remained controversial to date. Some studies report an association with OAB and/or detrusor over activity (DO). Recently the International Consultation on Incontinence-Research Society recommended new clinical research to be performed on this subject. We provide a systematic review of the literature to specify this recommendation. Literature search was performed in PubMed, Embase, Web of Science, Cochrane, Central, Cinahl, Academic Science Premier, Science Direct, and Wiley Online using a sensitive search string combination. All authors independently reviewed and scored full text papers and consensus about methodological quality was obtained according to Oxford Level of Evidence (LoE). Four hundred eighty seven abstracts were screened, 25 papers met all predefined inclusion selection criteria. Incidence figures of UPV varied between 2% and 95%. Studies are of poor methodological quality with Oxford LoE scores of 3B and 4. Measurement methods and techniques show a large variety. The above mentioned association of DO/OAB with UPV is however frequently reported. There exists a phenomenon of UPV, apart from DO, which may be a separate entity within OAB syndrome. Large variation in measurement techniques and patient populations hinders fundamental research as well as clinical progress. Clinical relevance of UPV and consequences for treatment therefore are yet to be established. Future prospective research with well-defined patient population and standardised urodynamic measurement techniques is needed. Results of standardized and objective evaluations should be compared to clinical signs and symptoms by validated questionnaires. Neurourol. Urodynam. 36:51-56, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  8. Codetection of Trichomonas vaginalis and Candida albicans by PCR in urine samples in a low-risk population attended in a clinic first level in central Veracruz, Mexico. (United States)

    López-Monteon, A; Gómez-Figueroa, F S; Ramos-Poceros, G; Guzmán-Gómez, D; Ramos-Ligonio, A


    The aim of this study is to estimate the prevalence of Trichomonas vaginalis and Candida albicans in low-risk patients treated at a first level clinic (primary health care represents the first level of contact of individuals, families, and the community with the system national health). Using a cross-sectional study in patients treated in clinical laboratory of the Sanitary District no. 7 of the city of Orizaba during the months June-July, 252 urine samples were collected for the identification of T. vaginalis and C. albicans by PCR. Furthermore, we analyzed the sociodemographic characteristics of the studied population. We observed an overall prevalence of 23.41% (95% CI 22.10-24.72) for T. vaginalis and 38.88% (95% CI 37.73-40.03) for C. albicans. There was also presence of coinfection in 14.28% (95% CI 13.10-15.46), which was associated with the presence of pain. Most of the positive cases were observed in women house-maker (80%, 95% CI 50.36-48.98). The results of this study provide evidence that the majority of positive cases observed in the studied population are presented in an asymptomatic form and usually are not associated with any risk factor.

  9. Clinical characteristics of the first cases of invasive candidiasis in China due to pan-echinocandin-resistant Candida tropicalis and Candida glabrata isolates with delineation of their resistance mechanisms (United States)

    Chen, Sharon CA; Wang, He; Kong, Fanrong; Chu, Yun-Zhuo; Xu, Ying-Chun


    Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People’s Republic of China with IC, one with infection caused by pan-echinocandin-resistant Candida tropicalis and the other by pan-echinocandin-resistant Candida glabrata. We also describe the mechanisms of drug resistance of these isolates. The echinocandin-resistant C. glabrata isolate was cultured from ascitic fluid of a 46-year-old male patient with intra-abdominal IC developing after surgery in 2012. This patient had had no prior antifungal exposure. The echinocandin-resistant C. tropicalis isolate was cultured from chest drainage fluid of a 60-year-old female patient with severe coronary disease and lung infection. Prior to culture and identification of the isolate, the patient had received micafungin treatment for 19 days. Both isolates were cross-resistant to micafungin, anidulafungin, and caspofungin, with minimum inhibitory concentration values of ≥2 µg/mL. The amino acid substitution E655K was found adjacent to the FKS2 HS1 region of the C. glabrata isolate, while the substitution S80P were found in the FKS1 HS1 region of the C. tropicalis isolate. This report highlights the emergence of echinocandin resistance in two important non-albicans Candida species. Although the overall prevalence of echinocandin resistance is low in the People’s Republic of China, monitoring of antifungal susceptibility trends in all Candida species is warranted.

  10. Promoting culturally competent chronic pain management using the clinically relevant continuum model. (United States)

    Monsivais, Diane B


    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Nonmotor Symptoms in Parkinson’s Disease in 2012: Relevant Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Anne Marie Bonnet


    Full Text Available Nonmotor symptoms (NMSs of Parkinson’s disease (PD are common, but they are often underrecognized in clinical practice, because of the lack of spontaneous complaints by the patients, and partly because of the absence of systematic questioning by the consulting physician. However, valid specific instruments for identification and assessment of these symptoms are available in 2012. The administration of the self-completed screening tool, NMSQuest, associated with questioning during the consultation, improves the diagnosis of NMSs. NMSs play a large role in degradation of quality of life. More relevant NMSs are described in this review, mood disorders, impulse control disorders, cognitive deficits, hallucinations, pain, sleep disorders, and dysautonomia.

  12. Blood lactate concentration after exposure to conducted energy weapons (including TASER® devices): is it clinically relevant? (United States)

    Jauchem, James R


    In previous studies, blood lactate concentration (BLac) consistently increased in anesthetized animals and in human subjects after exposures to TASER(®) conducted energy weapons (CEWs). Some have suggested the increased BLac would have detrimental consequences. In the current review, the following are evaluated: (a) the nature of muscle contractions due to CEWs, (b) general aspects of increased BLac, (c) previous studies of conventional neuromuscular electrical stimulation and CEW exposures, and (d) BLac in disease states. On the basis of these analyses, one can conclude that BLac, per se (independent of acidemia), would not be clinically relevant immediately after short-duration CEW applications, due to the short time course of any increase.

  13. Clinically applied medical ethnography: relevance to cultural competence in patient care. (United States)

    Engebretson, Joan


    Medical anthropology provides an excellent resource for nursing research that is relevant to clinical nursing. By expanding the understanding of ethnographic research beyond ethnicity, nurses can conduct research that explores patient's constructions and explanatory models of health and healing and how they make meaning out of chronic conditions and negotiate daily life. These findings can have applicability to culturally competent care at both the organizational or systems level, as well as in the patient/provider encounter. Individual patient care can be improved by applying ethnographic research findings to build provider expertise and then using a cultural negotiation process for individualized patient care. Copyright © 2011. Published by Elsevier Inc.

  14. Impact of glucose measurement processing delays on clinical accuracy and relevance. (United States)

    Jangam, Sujit R; Hayter, Gary; Dunn, Timothy C


    In a hospital setting, glucose is often measured from venous blood in the clinical laboratory. However, laboratory glucose measurements are typically not available in real time. In practice, turn-around times for laboratory measurements can be minutes to hours. This analysis assesses the impact of turn-around time on the effective clinical accuracy of laboratory measurements. Data obtained from an earlier study with 58 subjects with type 1 diabetes mellitus (T1DM) were used for this analysis. In the study, glucose measurements using a YSI glucose analyzer were obtained from venous blood samples every 15 min while the subjects were at the health care facility. To simulate delayed laboratory results, each YSI glucose value from a subject was paired with one from a later time point (from the same subject) separated by 15, 30, 45, and 60 min. To assess the clinical accuracy of a delayed YSI result relative to a real-time result, the percentage of YSI pairs that meet the International Organization for Standardization (ISO) 15197:2003(E) standard for glucose measurement accuracy (±15 mg/dl for blood glucose ISO 15197:2003(E) recommendation of 95%. The accuracy was less than 65% for delays of 60 min. This analysis suggests that processing delays in glucose measurements reduce the clinical relevance of results in patients with T1DM and may similarly degrade the clinical value of measurements in other patient populations. © 2013 Diabetes Technology Society.

  15. Refining Prognosis in Lung Cancer: A Report on the Quality and Relevance of Clinical Prognostic Tools. (United States)

    Mahar, Alyson L; Compton, Carolyn; McShane, Lisa M; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A


    Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biological, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. A systematic search of the scientific literature for clinical prognostic tools in lung cancer published from January 1, 1996 to January 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small-cell lung cancer. All tools for small-cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only 11 were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision points and prioritized inclusion of established prognostic factors over emerging factors. Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation.

  16. Candida-associated denture stomatitis


    Salerno, Carmen; Pascale, Michelangelo; Contaldo, María; Esposito, V.; Busciolano, Maurizio; Milillo, Lucio; Guida, Agostino; Petruzzi, Massimo; Serpico, Rosario


    Candida albicans is a dimorphic yeast strongly gram positive able to live as normal commensal organism in the oral cavity of healthy people. It is the yeast more frequently isolated in the oral cavity. Under local and systemic factors related to the host conditions, it becomes virulent and responsible of oral diseases known as oral candidiasis. It has been shown that the presence of denture is a predisposing factor to the onset of pathologies related to C. albicans. Clinical studies have ...

  17. Development of DNA probes for Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, L.L.; Hudson, J.B.


    An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both /sup 32/P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

  18. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan


    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non......-fasting TGs as a risk factor for CVD and provide a suggested classification of non-fasting TG concentration. Secondly, we sought to describe methodologies to evaluate postprandial TG using a fat tolerance test (FTT) in the clinic. Thirdly, we discuss the role of non-fasting lipids in the treatment...... of postprandial hyperlipemia. Finally, we provide a series of clinical recommendations relating to non-fasting TGs based on the consensus of the Expert Panel: 1). Elevated non-fasting TGs are a risk factor for CVD. 2). The desirable non-fasting TG concentration is...

  19. Clinical Empathy and Narrative Competence: The Relevance of Reading Talmudic Legends as Literary Fiction (United States)

    Davidson, John H.


    The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy. PMID:25973266

  20. Stem cell therapy for joint problems using the horse as a clinically relevant animal model

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Betts, Dean H.


    Research into articular cartilage is a surprisingly recent endeavour and much remains to be learned about the normal development of the synovial joint and its components that interplay in osteoarthritis and focal cartilage defects. Stem cell research is likely to contribute to the understanding...... of the developmental biology of synovial joints and their pathologies. Before human clinical trials are undertaken, stem cell-based therapies for non-life-threatening disorders should be evaluated for their safety and efficacy using animal models of spontaneous disease and not solely by the existing laboratory models...... of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

  1. Clinical Empathy and Narrative Competence: The Relevance of Reading Talmudic Legends as Literary Fiction

    Directory of Open Access Journals (Sweden)

    John H. Davidson


    Full Text Available The “curative potential” in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve “narrative competence” in discerning and acting in accord with their preferences and best interests. The “narrative medicine” model of shared “close reading of literature and reflective writing” among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM, broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah’s death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including—especially—beneficence, non-maleficence, and autonomy.

  2. Prevalence and clinical relevance of autoimmune neutropenia in patients with primary Sjögren's syndrome. (United States)

    Brito-Zerón, Pilar; Soria, Natalia; Muñoz, Sandra; Bové, Albert; Akasbi, Miriam; Belenguer, Rafael; Sisó, Antoni; Ramos-Casals, Manuel


    To analyze the prevalence of neutropenia in a large cohort of patients with primary Sjögren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes. The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (manifestations, neoplasia, and death. Ninety-nine (33%) patients had neutropenia during the follow-up, which was related to neoplasia or drugs in 9 (3%) patients and was considered idiopathic in the remaining 90 (30%). Patients with neutropenia had a lower mean age at diagnosis of SS (51.9 versus 59.4 years, P leukemia. Neutropenia should be considered a relevant hematologic finding of primary SS, due both to its elevated prevalence and to its clinical significance (close association with anti-Ro/La antibodies, coexistence with other cytopenias, and development of severe infections).

  3. Psychometric properties and clinical relevance of the adolescent sleep hygiene scale in Dutch adolescents. (United States)

    de Bruin, Eduard J; van Kampen, Ris K A; van Kooten, Tamar; Meijer, Anne Marie


    This study investigated reliability, validity, and clinical relevance of the Adolescent Sleep Hygiene Scale (ASHS) in Dutch adolescents. The Dutch translation of the ASHS was administered to 186 normal-sleeping adolescents and 112 adolescents with insomnia. Their sleep variables were measured using sleep logs and questionnaires. From the insomnia group, scores were also obtained after six weeks of cognitive behavioral therapy for insomnia (n=58) or waiting list (n=22). The full scale of the ASHS had acceptable internal consistency. The results showed moderate to strong correlations of the ASHS (domains) with sleep quality, sleep duration and chronic sleep reduction. Furthermore, the Dutch ASHS was able to discriminate between normal sleepers and adolescents with insomnia, and scores of adolescents with insomnia improved after treatment. These findings confirm the importance of sleep hygiene in adolescent sleep, and contribute to the validity of the ASHS and its applicability in research and clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Clinical empathy and narrative competence: the relevance of reading talmudic legends as literary fiction. (United States)

    Davidson, John H


    The "curative potential" in almost any clinical setting depends on a caregiver establishing and maintaining an empathic connection with patients so as to achieve "narrative competence" in discerning and acting in accord with their preferences and best interests. The "narrative medicine" model of shared "close reading of literature and reflective writing" among clinicians as a means of fostering a capacity for clinical empathy has gained validation with recent empirical studies demonstrating the enhancement of theory of mind (ToM), broadly conceived as empathy, in readers of literary fiction. Talmudic legends, like that of Rabbi Judah's death, are under-appreciated, relevant sources of literary fiction for these efforts. The limitations of narrative medicine are readily counterbalanced by simultaneously practiced attention to traditional bioethical principles, including-especially-beneficence, non-maleficence, and autonomy.

  5. Gene mutations versus clinically relevant phenotypes: lyso-Gb3 defines Fabry disease. (United States)

    Niemann, Markus; Rolfs, Arndt; Störk, Stefan; Bijnens, Bart; Breunig, Frank; Beer, Meinrad; Ertl, Georg; Wanner, Christoph; Weidemann, Frank


    Currently, no method is available to identify α-galactosidase A (agalA) mutations determining clinically relevant Fabry disease. In our largest European Fabry cohort, we investigated whether a biomarker, specific for the defect, could stratify persons at risk. A total of 124 individuals with agalA mutations were investigated with a comprehensive clinical workup, genetic analysis, and laboratory testing, including measurements of agalA activity and lyso-Gb3 (degradation product of the accumulating Gb3). Additionally, an extensive family screening with a clinical workup of relatives was performed. The patient population was divided into 2 samples: previously described mutations (n=72) and novel mutations (n=52). The patients with previously described mutations were subdivided into 2 groups: classical mutations, which were known to cause the classic type of Fabry disease with specific symptoms and a high risk for major events in all 3 main organs (heart, kidney, and central nervous system), and atypical mutations without the typical presentation. All patients with atypical mutations (n=17) had lower lyso-Gb3 levels than any of the patients with classical Fabry disease (n=55). A cutoff value of 2.7 ng/mL separated the 2 groups. Six out of 52 patients with novel mutations showed a lyso-Gb3 level characterization of patients with lyso-Gb3≥2.7 ng/mL suggested classical Fabry mutations in most of the patients (93%). Our data show that the biomarker lyso-Gb3 may identify the clinically relevant agalA mutations leading to Fabry disease.

  6. Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures. (United States)

    Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping


    Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Estimating clinically relevant mental disorders in a rural and an urban setting in postconflict Timor Leste. (United States)

    Silove, Derrick; Bateman, Catherine Robina; Brooks, Robert T; Fonseca, C Amaral Zulmira; Steel, Zachary; Rodger, James; Soosay, Ian; Fox, Greg; Patel, Vikram; Bauman, Adrian


    Epidemiologic studies undertaken in postconflict countries have focused primarily on trauma-related disorders. There is a need to include disabling psychotic disorders in order to plan clinical services in these settings. To estimate the prevalence of key clinical disorders in Timor Leste (East Timor), and to assess cultural factors that may influence help-seeking patterns. A 2-phase total population survey of 1544 adults in an urban and a rural area of Timor Leste. Phase 1 involved a household informant survey using indigenous terms to detect psychosis and a screen of all adults for posttraumatic stress disorder (PTSD) and symptoms of psychologic distress, including depression and anxiety. In phase 2, clinicians interviewed all those identified by household informants and half of those who screened positive in order to assign DSM-IV diagnoses. Disability, explanatory models, and perceived needs were also assessed. Phase 1: Demographic characteristics; trauma events and PTSD (Harvard Trauma Questionnaire); psychologic distress (Kessler-10 scale). Phase 2: Structured Clinical Interview for relevant DSM-IV diagnoses; the Global Assessment of Functioning Scale and the World Health Organization Disability Assessment Scales; and the modified Short Explanatory Model Interview. The household informant method in phase 1 detected mainly psychotic disorders, and the screen method detected PTSD and depression. Phase 2 yielded a DSM-IV point prevalence estimate of 5.1% (including psychosis, 1.35%; and PTSD, 1.47%). Psychotic disorders were most disabling, primarily attributed to supernatural causes and treated mainly by traditional healers. Those with depression and PTSD experienced substantial disability but had received little treatment. They attributed their mental problems to social and traumatic causes. Our 2-phase method proved effective for identifying the range of disorders relevant to planning clinical services in postconflict developing countries. The unmet needs of

  8. Clinical relevance of comorbidity in obsessive compulsive disorder: the Netherlands OCD Association study. (United States)

    Hofmeijer-Sevink, Mieke Klein; van Oppen, Patricia; van Megen, Harold J; Batelaan, Neeltje M; Cath, Danielle C; van der Wee, Nic J A; van den Hout, Marcel A; van Balkom, Anton J


    This study describes lifetime and current rates of comorbidity, its onset and its consequences in a large clinical sample of patients with obsessive compulsive disorder (OCD). A wide range of risk factors and clinical characteristics were also examined to determine whether pure OCD is different from OCD with current comorbidity. Finally, the temporal sequencing of the disorders was examined. Data were obtained from the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. A sample of 382 participants with current OCD (during the past month) was evaluated. Current comorbidity occurred in 55% of patients with OCD, while 78% suffered from lifetime comorbidity. Comorbidity is associated with more severe OCD, anxiety and depressive symptoms and more negative consequences on daily life. Multiple comorbid disorders often precede OCD and influence both its course and severity. Childhood trauma and neuroticism are vulnerability factors for the development of multiple comorbid disorders in OCD. It should be noted that causal inferences about the association between risk factors and OCD are precluded since our results were based on cross-sectional data. (Multiple) comorbidity in OCD is clinically relevant since it is associated with a specific pattern of vulnerability, with greater chronicity, with more severe OCD and more negative consequences on daily life. This indicates that the diagnosis and treatment of all comorbid disorders is clinically relevant, and clinicians should be especially aware of multiple disorders in cases of childhood trauma and high levels of neuroticism. Primary OCD has a different developmental and comorbidity pattern compared to secondary OCD. © 2013 Elsevier B.V. All rights reserved.

  9. Nurses in the clinical area: relevance of a PhD. (United States)

    Wilkes, Lesley M; Mohan, Shantala


    This project aimed to explore the application and relevance of a PhD to nurses working in the clinical area. The complexity of nursing practice requires clinical nurses to be competent as investigators and professional leaders who could help structure nursing practice in more efficient ways. Research proposes that a PhD offers Limited employment opportunities, is mainly research oriented and tends to direct a nurse away from the clinical field. A mixed method study design utilising surveys and interviews was chosen to collect data for this study. Participants were nurses with a doctoral degree working/having worked in a clinical area after obtaining their PhD Nurses were recruited through student databases from Australian universities that offer doctoral degrees in nursing and also by using a snowball sampling technique. The majority of the 19 nurses who participated in the study had: varied expectation of doing a PhD; maintained their clinical positions after obtaining their doctoral degree, considered that the degree helped them to obtain better jobs/promotions and acknowledged the value of the PhD in patient care, in improving research and informing health policy. This study has exposed the positive aspects of completing a PhD and identifies its constructive application in the clinical area. It is essential to provide support and opportunities for nurses working in the clinical area to pursue doctoral degrees in order to enable them to enhance knowledge and build confidence and leadership skills and contribute to the improvement of nursing practice and the continued development of the profession.

  10. Clinical relevance of and risk factors associated with medication administration time errors. (United States)

    Teunissen, Rick; Bos, Jacqueline; Pot, Hans; Pluim, Marien; Kramers, Cornelis


    The clinical relevance of and risk factors associated with errors related to medication administration time were studied. In this explorative study, 66 medication administration rounds were studied on two wards (surgery and neurology) of a hospital. Data on medication errors were collected using the blister collection method. The emptied packaging material of medication was collected after each round and compared with each patient's medication orders. Administration time errors were defined as medication administration (actual intake) occurring more than one hour before or after the prescribed time. Generalized estimating equations analysis was performed to study the correlation between medication administration errors and risk factors. Data from 129 patients were included in the study. Among these 129 patients, 2874 opportunities for error were recorded. The majority of opportunities for error occurred during the 7 a.m. round. Within the 2874 opportunities for errors, 10 administration time errors occurred for medications that might interact with food or another medication. Time of administration (noon and 3 p.m.), route of administration (injection or infusion), and frequency of administration (if necessary) had significant protective effects against the occurrence of administration time errors. The rectal route of administration was associated with a significant increase in the frequency of administration time errors compared with the oral route. A clinically relevant administration time error occurred in 2 cases (0.07%). Analysis of medication administration rounds found time errors to be the most common medication error.

  11. [Relevance of Vascular Trauma in Trauma Care - Impact on Clinical Course and Mortality]. (United States)

    Lech, L; Jerkku, T; Kanz, K-G; Wierer, M; Mutschler, W; Koeppel, T A; Lefering, R; Banafsche, R


    There is a lack of evidence as to the relevance of vascular trauma (VT) in patients with severe injuries. Therefore, we reviewed registry data in the present study in order to systematically objectify the effect of VT in these patients. This study aimed to provide an adequate picture of the relevance of vascular trauma and to identify adverse prognostic factors. In a retrospective analysis of records from the TraumaRegister DGU® (TR-DGU) in two subgroups with moderate and severe VT, we examined the records for differences in terms of morbidity, mortality, follow-up and prognostic parameters compared to patients without VT with the same ISS. From a total of 42,326 patients, 2,961 (7 %) had a VT, and in 2,437 cases a severe VT (AIS ≥ 3) was diagnosed (5.8 %). In addition to a higher incidence of shock and a 2 to 3-fold increase in fluid replacement and erythrocyte transfusion, patients with severe VT had a 60 % higher rate of multiple organ failure, and in-hospital mortality was twice as high (33.8 %). The massively increased early mortality (8.0 vs. 25.2 %) clearly illustrates how severely injured patients are placed at risk by the presence of a relevant VT with a comparable ISS. In our opinion, due to an unexpected poor prognosis in the TR-DGU data for vascular injuries, increased attention is required in the care of severely injured patients. Based on our comprehensive analysis of negative prognostic factors, a further adjustment to the standards of vascular medicine could be advisable. The influence of the level of care provided by the admitting hospital and the relevance of a further hospital transfer to prognosis and clinical outcome is currently being analysed. Georg Thieme Verlag KG Stuttgart · New York.

  12. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine. (United States)

    Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří


    Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach), a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

  13. Responding to the challenge of clinically relevant osteopathic research: efficacy and beyond (United States)

    Licciardone, John C.


    The osteopathic profession has been challenged over the past decade to provide clinically relevant research. The conduct of evidence-based osteopathic research is imperative not only for scientific, economic, and professional reasons, but also to drive health care policy and clinical practice guidelines. This paper summarizes recent studies in response to the osteopathic research challenge, including clinical trials registered with and a systematic review and meta-analysis of osteopathic manipulative treatment (OMT) for low back pain. The concept of the OMT responder is introduced and supported with preliminary data. Within the context of a pain processing model, consideration is given to genomic (e.g., the catechol-O-methyltransferase gene) and psychological (e.g., depression and somatization) factors that are associated with pain sensitivity and pain progression, and to the role that such factors may play in screening for OMT responders. While substantial progress has been made in osteopathic research, much more needs to be done. PMID:18311324

  14. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. (United States)

    Lisowski, Leszek; Dane, Allison P; Chu, Kirk; Zhang, Yue; Cunningham, Sharon C; Wilson, Elizabeth M; Nygaard, Sean; Grompe, Markus; Alexander, Ian E; Kay, Mark A


    Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials. The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome. Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human-murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo. As predicted from preclinical and clinical studies, rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly-approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.

  15. Antifungal Activity of Thapsia villosa Essential Oil against Candida, Cryptococcus, Malassezia, Aspergillus and Dermatophyte Species

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    Eugénia Pinto


    Full Text Available The composition of the essential oil (EO of Thapsia villosa (Apiaceae, isolated by hydrodistillation from the plant’s aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5% and methyleugenol (35.9%, were evaluated against clinically relevant yeasts (Candida spp., Cryptococcus neoformans and Malassezia furfur and moulds (Aspergillus spp. and dermatophytes. Minimum inhibitory concentrations (MICs were measured according to the broth macrodilution protocols by Clinical and Laboratory Standards Institute (CLSI. The EO, limonene and methyleugenol displayed low MIC and MFC (minimum fungicidal concentration values against Candida spp., Cryptococcus neoformans, dermatophytes, and Aspergillus spp. Regarding Candida species, an inhibition of yeast–mycelium transition was demonstrated at sub-inhibitory concentrations of the EO (MIC/128; 0.01 μL/mL and their major compounds in Candida albicans. Fluconazole does not show this activity, and the combination with low concentrations of EO could associate a supplementary target for the antifungal activity. The association of fluconazole with T. villosa oil does not show antagonism, but the combination limonene/fluconazole displays synergism. The fungistatic and fungicidal activities revealed by T. villosa EO and its main compounds, associated with their low haemolytic activity, confirm their potential antimicrobial interest against fungal species often associated with human mycoses.

  16. Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains of Candida glabrata

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    Maria Helena Galdino Figueiredo-Carvalho


    Full Text Available Candida glabrata is a facultative intracellular opportunistic fungal pathogen in human infections. Several virulence-associated attributes are involved in its pathogenesis, host-pathogen interactions, modulation of host immune defenses, and regulation of antifungal drug resistance. This study evaluated the in vitro antifungal susceptibility profile to five antifungal agents, the production of seven hydrolytic enzymes related to virulence, and the relationship between these phenotypes in 91 clinical strains of C. glabrata. All C. glabrata strains were susceptible to flucytosine. However, some of these strains showed resistance to amphotericin B (9.9%, fluconazole (15.4%, itraconazole (5.5%, or micafungin (15.4%. Overall, C. glabrata strains were good producers of catalase, aspartic protease, esterase, phytase, and hemolysin. However, caseinase and phospholipase in vitro activities were not detected. Statistically significant correlations were identified between micafungin minimum inhibitory concentration (MIC and esterase production, between fluconazole and micafungin MIC and hemolytic activity, and between amphotericin B MIC and phytase production. These results contribute to clarify some of the C. glabrata mechanisms of pathogenicity. Moreover, the association between some virulence attributes and the regulation of antifungal resistance encourage the development of new therapeutic strategies involving virulence mechanisms as potential targets for effective antifungal drug development for the treatment of C. glabrata infections.

  17. [Aspergillus fumigatus and Candida albicans in cystic fibrosis: clinical significance and specific immune response involving serum immunoglobulins G, A, and M]. (United States)

    Máiz, Luis; Cuevas, Manuela; Lamas, Adelaida; Sousa, Aurora; Quirce, Santiago; Suárez, Lucrecia


    The aim of this study was to analyze the clinical significance of Aspergillus fumigatus and Candida albicans in respiratory secretions from patients with cystic fibrosis and to assess the immune response to these fungi in serum. The study included 66 patients with cystic fibrosis (34 men; mean age, 16.2 years). Sera from 15 healthy individuals were used as controls. The serum concentrations of immunoglobulin (Ig) G, IgA, and IgM against A fumigatus and C albicans were higher in patients than in the control group. There was no correlation between the presence of A fumigatus in respiratory secretions and the immune response to the fungus measured in serum. In contrast, the presence of C albicans in respiratory secretions was correlated with the immune response to that fungus. The likelihood of obtaining A fumigatus cultures from respiratory secretions increased with age. The presence of these fungi in respiratory samples was not a risk factor for greater respiratory impairment. In response to increased colonization of the lower respiratory tract by A fumigatus and C albicans, patients with cystic fibrosis have elevated serum levels of IgG, IgA, and IgM against those fungi. In patients with cystic fibrosis, culture of sputum and oropharyngeal secretions is adequate for the assessment of lower respiratory tract colonization by C albicans but not A fumigatus. Fungal colonization of the lower respiratory tract is not a risk factor for greater respiratory impairment in patients with cystic fibrosis.

  18. [Candida: epidemiology and risk factors for non-albicans species]. (United States)

    Cornistein, Wanda; Mora, Andrea; Orellana, Nora; Capparelli, Federico Javier; del Castillo, Marcelo


    Nosocomial fungal infections have increased significantly in the last decade. Candida detection in clinical specimens can mean either colonization or an infection which can be local (muguet) or invasive. Knowledge of the species helps in choosing the best treatment. The aims of this study were to determine the frequency and distribution of Candida species detected in clinical samples, to analyze the clinical characteristics of the involved population and to determine the risk factors for Candida non-albicans species. Retrospective, observational. 2006-2010. all isolates of Candida in clinical specimens from patients hospitalized at least 48 hours in a neurological center. We analyzed epidemiological characteristics, co morbidities, risk factors, factors associated with Candida non-albicans detection, antifungal treatment, development of adverse events and mortality. Candida spp. was isolated from 321 clinical specimens: 139 (43.3%) were C. albicans and 182 (56.7%) Candida non-albicans. The distribution of the sample was: urine 122 (Candida non-albicans 67.2%), airway 81, oropharynx 45 (C. albicans) and candidemia 40 (Candida non-albicans 75%). The most frequent co-morbidity was solid tumor (35.5%). The main risk factors were antibiotic therapy (85.5%), steroid therapy (61.7%) and in ICU at diagnosis (61.6%). The analysis of risk factors and the isolation of Candida non-albicans shows that chemotherapy, previous surgery, treatment with aminopenicillins, carbapenems and glycopeptides were statistically significant (PCandida species distribution varies with the type of sample analyzed. Non-albicans species make up the majority of the isolates. The identification of the species involved per sample helps to optimize treatment. The high frequency of isolation of Candida in patients on steroids and antibiotics and admitted to ICU, is worth pointing out. Patients with previous surgery, treated with the aforementioned antibiotics or chemotherapy, could receive non

  19. Psychiatric disorders in children and adolescents presenting with unexplained chronic pain: what is the prevalence and clinical relevancy?

    NARCIS (Netherlands)

    Knook, L.M.; Konijnenberg, A.Y.; Hoeven, J. van der; Kimpen, J.L.L.; Buitelaar, J.K.; Engeland, H. van; Graeff-Meeder, E.R. de


    The prevalence of psychiatric disorders among children with unexplained chronic pain (UCP) is high in unselected populations and pain clinics, yet the clinical relevance of these disorders in children referred for unexplained pain is not known. This study assessed the prevalence of clinically

  20. Clinically Relevant Injury Patterns After an Anterior Cruciate Ligament Injury Provide Insight Into Injury Mechanisms (United States)

    Levine, Jason W.; Kiapour, Ata M.; Quatman, Carmen E.; Wordeman, Samuel C.; Goel, Vijay K.; Hewett, Timothy E.; Demetropoulos, Constantine K.


    Background The functional disability and high costs of treating anterior cruciate ligament (ACL) injuries have generated a great deal of interest in understanding the mechanism of noncontact ACL injuries. Secondary bone bruises have been reported in over 80% of partial and complete ACL ruptures. Purpose The objectives of this study were (1) to quantify ACL strain under a range of physiologically relevant loading conditions and (2) to evaluate soft tissue and bony injury patterns associated with applied loading conditions thought to be responsible for many noncontact ACL injuries. Study Design Controlled laboratory study. Methods Seventeen cadaveric legs (age, 45 ± 7 years; 9 female and 8 male) were tested utilizing a custom-designed drop stand to simulate landing. Specimens were randomly assigned between 2 loading groups that evaluated ACL strain under either knee abduction or internal tibial rotation moments. In each group, combinations of anterior tibial shear force, and knee abduction and internal tibial rotation moments under axial impact loading were applied sequentially until failure. Specimens were tested at 25° of flexion under simulated 1200-N quadriceps and 800-N hamstring loads. A differential variable reluctance transducer was used to calculate ACL strain across the anteromedial bundle. A general linear model was used to compare peak ACL strain at failure. Correlations between simulated knee injury patterns and loading conditions were evaluated by the χ2 test for independence. Results Anterior cruciate ligament failure was generated in 15 of 17 specimens (88%). A clinically relevant distribution of failure patterns was observed including medial collateral ligament tears and damage to the menisci, cartilage, and subchondral bone. Only abduction significantly contributed to calculated peak ACL strain at failure (P = .002). While ACL disruption patterns were independent of the loading mechanism, tibial plateau injury patterns (locations) were

  1. Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms. (United States)

    Manzardo, Ann M; McGuire, Austen; Butler, Merlin G


    Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence. We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form. We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG). High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism

  2. Clinically relevant magnetic resonance imaging (MRI findings in elite swimmers’ shoulders

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    Arno Celliers


    Full Text Available Background: Shoulder pain is the most common and well-documented site of musculoskeletal pain in elite swimmers. Structural abnormalities on magnetic resonance imaging (MRI of elite swimmers’ symptomatic shoulders are common. Little has been documented about the association between MRI findings in the asymptomatic shoulder versus the symptomatic shoulder.Objective: To assess clinically relevant MRI findings in the shoulders of symptomatic and asymptomatic elite swimmers.Method: Twenty (aged 16–23 years elite swimmers completed questionnaires on their swimming training, pain and shoulder function. MRI of both shoulders (n = 40 were performed and all swimmers were given a standardised clinical shoulder examination. Results: Both shoulders of 11 male and 9 female elite swimmers (n = 40 were examined. Eleven of the 40 shoulders were clinically symptomatic and 29 were asymptomatic. The most common clinical finding in both the symptomatic and asymptomatic shoulders was impingement during internal rotation, with impingement in 54.5% of the symptomatic shoulders and in 31.0% of the asymptomatic shoulders. The most common MRI findings in the symptomatic and asymptomatic shoulders were supraspinatus tendinosis (45.5% vs. 20.7%, subacromial subdeltoid fluid (45.5% vs. 34.5%, increased signal in the AC Joint (45.5% vs. 37.9% and AC joint arthrosis (36.4% vs. 34.5%. Thirty-nine (97.5% of the shoulders showed abnormal MRI features.Conclusion: MRI findings in the symptomatic and asymptomatic shoulders of young elite swimmers are similar and care should be taken when reporting shoulder MRIs in these athletes. Asymptomatic shoulders demonstrate manifold MRI abnormalities that may be radiologically significant but appear not to be clinically significant.

  3. Isolation, speciation, and antibiogram of clinically relevant non-diphtherial Corynebacteria (Diphtheroids

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    B S Reddy


    Full Text Available Purpose: Coryneform or the non-diphtherial Corynebacterium species largely remains a neglected group with the traditional consideration of these organisms as contaminants. This concept, however, is slowly changing in the light of recent observations. This study has been done to find out the species distribution and antibiogram of various members of the clinically relevant Coryneform group, isolated from various clinical materials. Materials and Methods: One hundred and fourteen non-duplicate isolates of diphtheroids from various clinical isolates were selected for the study. The isolates were identified to the species level by using a battery of tests; and antimicrobial susceptibility was tested by using a combination of Clinical and Laboratory Standards Institute (CLSI and the British Society for Antimicrobial Chemotherapy (BSAC guidelines, in the absence of definitive CLSI guidelines. Results: Corynebacterium amycolatum was the predominant species (35.9% in our series followed by the CDC Group G organisms (15.7%. Each of the remaining 19 species comprised of less than 10% of the isolates. More than half the total isolates were resistant to the penicillins, erythromycin, and clindamycin; while excellent activity (all the strains being susceptible was shown by vancomycin, linezolid, and tigecycline. Chloramphenicol and tetracycline also had good activity in inhibiting more than 80% of the isolates. Multiply drug resistance was exhibited by all the species. Conclusion: This study was an attempt to establish the clinical significance of coryneform organisms. The high level of resistance shown by this group to some of the common antibacterial agents highlights the importance of processing these isolates in select conditions to guide the clinicians towards an appropriate therapy.

  4. Update on cardiovascular safety of PPARgamma agonists and relevance to medicinal chemistry and clinical pharmacology. (United States)

    Ciudin, Andreea; Hernandez, Cristina; Simó, Rafael


    Peroxisome proliferator-activator receptors (PPARs) are now known as members of the nuclear hormonereceptor superfamily of ligand-activated transcription factors that regulate gene expression in response to nutritional and physiological stimuli. PPARγ plays a crucial role in glucose homeostasis and it is involved in the regulation of lipid metabolism and adipocyte differentiation and function. From all the PAARγ ligands, the thiazolidindiones (TZDs) are of most clinical importance. Rosiglitazone and pioglitazone have been largely used so far in the clinical practice. They provide similar effects on glycemic control, as well as a range of similar adverse effects, such as weight gain, fluid retention, and increased risk of hearth failure, which seem to be PPARγ mediated. Interestingly, they differ on their effect on lipid and cardiovascular safety profile, indicating a PPARγ-independent mechanism. Indeed, rosiglitazone was recently withdrawn in Europe and its use has been restricted in USA as a consequence of increased risk of cardiovascular events in type 2 diabetic patients. This review is focused on the cardiovascular effects of rosiglitazone and pioglitazone as representative members of PPARγ ligands, because they were widely evaluated in many clinical trials and experimental studies and data obtained from these studies are relevant from medicinal chemistry and clinical pharmacology point of view. Finally, an overview on the development of selective PPARγ modulators and/or dual PPARα/γ agonists will be given. These new approaches might provide anti-hyperglycemic efficacy without the associated undesirable side-effects. However, further experimental and clinical studies evaluating the theoretical benefit and safety of this therapeutic strategy are needed.

  5. Relevance of Plasma Cholinesterase to Clinical Findings in Acute Organophosphorous Poisoning

    Directory of Open Access Journals (Sweden)

    Devanur R.M.M. Prasad


    Full Text Available Background: Organophosphorus (OP poisoning is a major public health problem in developing world. OP pesticides inhibit carboxylic esterase enzymes including plasma cholinesterase (PChE. Clinical manifestations following OP poisoning can be associated with the extent of decrease of PChE. This study was designed to investigate the relevance of PChE level to clinical manifestations in OP poisoning and to evaluate usefulness of PChE in predicting clinical outcomes. Methods: This was a cross-sectional study which was conducted at Jawaharlal Nehru Medical College, Karnataka from 1st October 2009 to 30th September 2010. Seventy-six OP poisoned patients were enrolled and their clinical manifestations were recorded. 5-ml samples of intravenous blood were collected from each patient (on first day and fifth day of treatment under strict aseptic precaution and the PChE level was measured. Results: In total, mean age of patients were 25.5 (range: 21-30 years. Majority of patients were males (65.7 %, from rural areas (86.84 % and agricultural workers (25%. Main clinical findings at the time of admission were congested conjunctiva (87%, pin point pupil (83%, lacrimation (80%, vomiting (78%, non-reactive pupil (75%, respiratory distress (60% and abdominal pain (37%. Mean (SD PChE at 6 hours post-exposure was 3672.4 (4200.1 IU/L. At presentation, cyanosis, muscle weakness, convulsion, respiratory distress and fasciculation were related to cases with >75%reduction of PChE, while,  constricted and non-reactive pupil, lacrimation and congested conjunctivae were related to cases with 50-75% reduction and abdominal pain, dryness of conjunctiva, vomiting and diarrhea were related to

  6. [Monitoring of pain, nociception, and analgesia under general anesthesia: Relevance, current scientific status, and clinical practice]. (United States)

    von Dincklage, F


    To avoid negative effects of painful stimuli under general anesthesia, an adequate analgesia is needed. Since both overdosing and underdosing of analgesics may lead to negative consequences, an optimal dosing is crucial, requiring a continuous monitoring of the balance between the ongoing nociception and the level of analgesia. This review describes current methods for the monitoring of nociception and analgesia as well as their inherent differences. Monitors of nociception register organic responses that are triggered through painful stimuli and therefore allow the detection of phases of excessive nociception during inadequate analgesia. In contrast, monitors of analgesia register nociception-specific organic responses that are triggered through test stimuli and allow a preemptive adaption of the level of analgesia, before a painful clinical stimulus is applied, but require the application of test stimuli. Preliminary proof-of-concept studies were able to demonstrate the potential of the here described methods; however, an effect on the clinical outcome of patients has not yet been shown for either of the two types of monitoring. For the routine application of monitors of nociception and analgesia in daily clinical practice, large clinical studies are necessary, proving a positive outcome effect. Without reliable parameters for nociception and analgesia it was hitherto impossible to perform such studies. The progress made in recent years generates optimism that in the not too distant future the currently available methods to monitor nociception and analgesia might improve to a level of reliability to allow them to be used to investigate the clinical outcome relevance of nociception and analgesia.

  7. Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

    Directory of Open Access Journals (Sweden)

    Naoki Hayashi

    Full Text Available Suicidal behavior (SB is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct.To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance.By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA.Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT, Interpersonal-change (IC, Self-renunciation (SR and Self-sustenance (SS. These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively.The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part

  8. Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients. (United States)

    Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji


    Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the

  9. Polanyi's tacit knowing and the relevance of epistemology to clinical medicine. (United States)

    Henry, Stephen G


    Most clinicians take for granted a simple, reductionist understanding of medical knowledge that is at odds with how they actually practice medicine; routine medical decisions incorporate more complicated kinds of information than most standard accounts of medical reasoning suggest. A better understanding of the structure and function of knowledge in medicine can lead to practical improvements in clinical medicine. This understanding requires some familiarity with epistemology, the study of knowledge and its structure, in medicine. Michael Polanyi's theory of tacit knowing is advanced as the basis for developing a more accurate understanding of medical knowledge. Tacit knowing, which explores the taken-for-granted background knowledge that underlies all human knowing, is explained in detail with a focus on its relevance for clinical medicine. The implications of recognizing tacit knowing in medicine and medical decisions are discussed. These include the ability to explain the importance of the clinical encounter in medical practice, mechanisms for analysing patient and doctor as persons, and the need for humility given the uncertainty that the tacit dimension injects into all medical decisions. This more robust medical epistemology allows clinicians to better articulate the nature and importance of patient-centred care, to avoid pitfalls inherent in reductionist approaches to medical knowledge, and to think more clearly about the relationships between medicine and health care at the individual and population levels.

  10. PET-CT manifestation of Candida esophagitis

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    Bahk, Yong Whee [Sung-Ae Hospital, Seoul (Korea, Republic of); O, Joo Hyun [Kangnam St. Mary' s Hospital, Catholic University Medical School, Seoul (Korea, Republic of)


    Candida esophagitis (moniliasis) is the most common infection of the gullet and has generally been attributed to as a complication of immune suppressed state. However, as the current case. Holt found the disease to occur in 3 of his 13 patients without predisposing condition. Predisposing factors other than immune deficient conditions include aplastic anemia, alcoholism and Parkinson's disease and age, diabetes mellitus, and disruption of mucosal integrity. Growing prevalence of Candida esophagitis in recent years is accounted for by an increase in the number of patients with organ transplantation, malignancy and AIDS as well as populrization of endoscopy. Microorganisms that reached the esophagus in oral secretions are rarely cultured from the esophageal surface. Of many species C. albicans is the most common offender although C. tropicalis has also been isolated with high prevalence, particularly in the patients with cancer and disseminated candidiasis. Clinically, the patients with Candida esophagitis seek medical care for esophageal or retrosternal pain, dysphagia or distress. Candida esophagitis may be the extension from oropharyngeal infection but in the majority the esophagus is the sole site of infection. The middle and lower thirds of the esophagus are more typically affected than the upper third. Diagnosis can be indicated by double contrast esophagography or endoscopy and confirmed by potassium hydroxide (KOH) stain or biopsy. It is to be noted that the more presence of Candida in smear or cultured specimen cannot indict Candida as definitive offender. Differential diagnosis includes herpes simplex infection, cytomegalovirus infection, reflux esophagitis or radiation esophagitis.

  11. Candida infection in oral leukoplakia: an unperceived public health problem. (United States)

    Dilhari, Ayomi; Weerasekera, Manjula M; Siriwardhana, Anusha; Maheshika, Oshanthi; Gunasekara, Chinthika; Karunathilaka, Sunil; Nagahawatte, Ajith; Fernando, Neluka


    The study aimed to determine the proportion, known risk factors and etiology for Candida infection in leukoplakia lesions among patients with oral leukoplakia attending the Oral and Maxillofacial Clinic at a Tertiary Care Hospital in Sri Lanka. Eighty clinically suspected oral leukoplakia patients were included. Two oral swabs each, from leukoplakia patients: one swab from the lesion and the other one from the contralateral unaffected corresponding area (as a control) were collected. Direct microscopy and culture followed by colony count and phenotypic identification were performed to identify pathogenic Candida species. Candida infection was seen in 47% of patients with oral leukoplakia. Candida albicans (94.7%) was the most common Candida species followed by Candida tropicalis (5.3%). Majority of Candida-infected lesions were seen in the buccal mucosa region. Alteration of taste (p = 0.021), having other oral lesions (p = 0.008), angular cheilitis (p = 0.024) and periodontitis (p = 0.041) showed a significant association with Candida-associated leukoplakia. Increasing age showed a significant tendency for Candida infection (p = 0.020). Smoking (p = 0.026) and betel-quid chewing (p = 0.006) were also found to be significantly associated, although alcohol consumption alone did not show a significant association. Oral leukoplakia patients who had all three habits: alcohol consumption, smoking and betel-quid chewing had a significant association with Candida infection (p = 0.004). Patients who had a combination of risk factors: smoking, betel-quid chewing and alcohol consumption were seen to have a significant association with Candida infection. Further betel-quid chewing alone and smoking singly was also significantly associated with Candida infection in oral leukoplakia.

  12. Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease (United States)

    Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.


    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. PMID:23428415

  13. Markers of oxidant stress that are clinically relevant in aging and age-related disease. (United States)

    Jacob, Kimberly D; Noren Hooten, Nicole; Trzeciak, Andrzej R; Evans, Michele K


    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. Published by Elsevier Ireland Ltd.

  14. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease. (United States)

    Diana, T; Krause, J; Olivo, P D; König, J; Kanitz, M; Decallonne, B; Kahaly, G J


    The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P  70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism. © 2017 British Society for Immunology.

  15. Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance. (United States)

    Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan


    Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email:

  16. Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance. (United States)

    Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali


    The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

  17. In Vivo Photoacoustic and Fluorescence Cystography Using Clinically Relevant Dual Modal Indocyanine Green

    Directory of Open Access Journals (Sweden)

    Sungjo Park


    Full Text Available Conventional X-ray-based cystography uses radio-opaque materials, but this method uses harmful ionizing radiation and is not sensitive. In this study, we demonstrate nonionizing and noninvasive photoacoustic (PA and fluorescence (FL cystography using clinically relevant indocyanine green (ICG in vivo. After transurethral injection of ICG into rats through a catheter, their bladders were photoacoustically and fluorescently visualized. A deeply positioned bladder below the skin surface (i.e., ~1.5–5 mm was clearly visible in the PA and FL image using a laser pulse energy of less than 2 mJ/cm2 (1/15 of the safety limit. Then, the in vivo imaging results were validated through in situ studies. Our results suggest that dual modal cystography can provide a nonionizing and noninvasive imaging tool for bladder mapping.

  18. Photonics-based in vivo total hemoglobin monitoring and clinical relevance. (United States)

    McMurdy, John; Jay, Gregory; Suner, Selim; Crawford, Gregory


    Anemia is a serious disorder which, as a result of antiquated invasive blood testing, is undiagnosed in millions of people in the U.S. As a result of the clinical need, many technological solutions have been proposed to measure total blood hemoglobin, and thus diagnose anemia, noninvasively. Because hemoglobin is the strongest chromophore in tissue, spectroscopic methods have been the most prevalently investigated. Difficulties in extracting a quantitative estimation of hemoglobin based on tissue absorption include variability in the absorption spectra of hemoglobin derivatives, interference from other tissue chromophores, and interpatient physiological variations affecting the effective optical path length of light propagating in tissue. In spite of these challenges, studies with a high degree of correlation between in vitro and in vivo measured total hemoglobin have been disclosed using variants of transmission and diffuse reflection spectroscopy in assorted physiological locations. A review of these technologies and the relevant advantages/disadvantages are presented here.

  19. Assessing Hospital Physicians' Acceptance of Clinical Information Systems: A Review of the Relevant Literature

    Directory of Open Access Journals (Sweden)

    Bram Pynoo


    Full Text Available In view of the tremendous potential benefits of clinical information systems (CIS for the quality of patient care; it is hard to understand why not every CIS is embraced by its targeted users, the physicians. The aim of this study is to propose a framework for assessing hospital physicians' CIS-acceptance that can serve as a guidance for future research into this area. Hereto, a review of the relevant literature was performed in the ISI Web-of-Science database. Eleven studies were withheld from an initial dataset of 797 articles. Results show that just as in business settings, there are four core groups of variables that influence physicians' acceptance of a CIS: its usefulness and ease of use, social norms, and factors in the working environment that facilitate use of the CIS (such as providing computers/workstations, compatibility between the new and existing system.... We also identified some additional variables as predictors of CIS-acceptance.

  20. Advances on the molecular characterization, clinical relevance, and detection methods of Gadiform parvalbumin allergens. (United States)

    Fernandes, Telmo J R; Costa, Joana; Carrapatoso, Isabel; Oliveira, Maria Beatriz P P; Mafra, Isabel


    Gadiform order includes several fish families, from which Gadidae and Merlucciidae are part of, comprising the most commercially important and highly appreciated fish species, such as cod, pollock, haddock, and hake. Parvalbumins, classified as calcium-binding proteins, are considered the main components involved in the majority of fish allergies. Nine and thirteen parvalbumins were identified in different fish species from Gadidae and Merlucciidae families, respectively. This review intends to describe their molecular characterization and the clinical relevance, as well as the prevalence of fish allergy. In addition, the main protein- and DNA-based methods to detect fish allergens are fully reviewed owing to their importance in the safeguard of sensitized/allergic individuals.

  1. Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

    DEFF Research Database (Denmark)

    Du, Peina; Huang, Peide; Huang, Xuanlin


    was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC....... Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more...... and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients....

  2. Peripheral Blood Mononuclear Cells Spontaneous Osteoclastogenesis: Mechanisms Driving the Process and Clinical Relevance in Skeletal Disease. (United States)

    Salamanna, Francesca; Maglio, Melania; Borsari, Veronica; Giavaresi, Gianluca; Aldini, Nicolò Nicoli; Fini, Milena


    In vitro peripheral blood mononuclear cells differentiate into osteoclasts under the influence of osteoclast-stimulating factors. However, accumulating evidence suggests spontaneous osteoclasts formation and activity in patients affected by local or systemic bone remodeling diseases in comparison with healthy controls. Therefore, within this review, we summarize the studies where spontaneous osteoclastogenesis of peripheral blood mononuclear cells was observed in pathological conditions of the skeletal system. We indicate a linkage between immunoregulation by T cells and spontaneous osteoclasts formation with increased levels of tumor necrosis factors-α, receptor activator of nuclear factor kappa-B ligand and inteleukin-7 production. In the light of these results, it would be of crucial importance to deepen the correlation between systemic bone remodeling diseases and spontaneous osteoclastogenesis as well as to investigate in detail the mechanisms underlying this phenomenon and the clinical relevance in bone remodeling disease diagnosis and monitoring. © 2015 Wiley Periodicals, Inc.

  3. Clinically relevant pain relief with an ibuprofen-releasing foam dressing

    DEFF Research Database (Denmark)

    Fogh, Karsten; Andersen, Maibritt B; Bischoff-Mikkelsen, Morten


    The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary......) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p...... = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen...

  4. Antifungal Effect of Novel 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl-1-phenylethanone against Candida strains

    Directory of Open Access Journals (Sweden)

    Monika Staniszewska


    Full Text Available We investigated the antifungal activity of novel a 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl-1-phenylethanone (compound 4. The synthesis of compound 4 was commenced from sodium 4-chlorobenzene sulfinate and the final product was obtained by treatment of β-chloro β-keto-sulfone with sodium hypobromite. The sensitivity of sixty three clinical isolates belonging to the most relevant Candida species towards compound 4 using the method M27-A3 was evaluated. We observed among most of the clinical strains of C. albicans MIC ranging from 0.00195 to 0.0078 µg/mL. Compound 4 at 32 μg/mL exhibited fungicidal activity against nine Candida strains tested using the MFC assay. Compound 4 displayed anti-Candida activity (with clear endpoint against 22% of clinical strains of Candida. Under compound 4, Candida susceptibility and tolerance, namely paradoxical effect (PG, was found for only two clinical isolates (C. glabrata and C. parapsilosis and reference strain 14053 using both M27-A3 and MFC method. We found that compound 4 does not induce toxicity in vivo against larvae of Galleria mellonella (≥97% survival and it displays reduced toxicity on mammalian cells in vitro (Candida strains.

  5. Clinical and Laboratory Features of Six Cases of Candida and Dermatophyte Folliculitis and a Review of Published Studies

    NARCIS (Netherlands)

    Durdu, M.; Guran, M.; Kandemir, H.; Ilkit, M.; Seyedmousavi, S.


    Although some studies have investigated the epidemiological characteristics of Malassezia folliculitis (MF), little is known about the clinical features and laboratory characteristics of folliculitis caused by other fungi. In this prospective study, 158 patients with folliculitis were identified,

  6. What efficacy measures are clinically relevant and should be used in Cochrane Reviews of acute migraine trials?

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer


    BACKGROUND: Cochrane Reviews are methodologically of high quality but the clinical relevance of analysed efficacy measures (EMs) should also be assessed. METHODS: The clinical relevance of EMs used in one systematic Cochrane review of oral zolmitriptan for migraine headache was evaluated. RESULTS......: The following EMs were used: pain free at two hours (30%), headache relief at two hours (60%), sustained pain free for 24 hours (19%) and sustained headache relief for 24 hours (39%). These EMs were also used in four other Cochrane reviews of acute migraine treatment. Of these EMs sustained headache relief...... for 24 h is not judged clinically relevant. CONCLUSION: Pain free and sustained pain free are clinically relevant, but the responses are rather low, demonstrating that there is a need for improvement of acute drug treatment in migraine....

  7. Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

    Energy Technology Data Exchange (ETDEWEB)

    Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A. [Canis Lupus LLC and Department of Human Oncology, University of Wisconsin, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Departments of Human Oncology, Medical Physics, and Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53792 (United States)


    Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa

  8. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR


    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  9. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis. (United States)

    Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L


    Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Hyphal content determines the compression strength of Candida albicans biofilms

    NARCIS (Netherlands)

    Paramonova, Ekaterina; Krom, Bastiaan P.; van der Mei, Henny C.; Busscher, Henk J.; Sharma, Prashant K.

    Candida albicans is the most frequently isolated human fungal pathogen among species causing biofilm-related clinical infections. Mechanical properties of Candida biofilms have hitherto been given no attention, despite the fact that mechanical properties are important for selection of treatment or

  11. Identification of Candida strains isolated from Tanzanian pregnant ...

    African Journals Online (AJOL)

    Objective: To identify Candida strains isolated from Tanzanian women (13 to 45 years) with vaginal candidiasis. Design: A cross-sectional study. Setting: Antenatal clinic in llala district hospital in Dar es Salaam, Tanzania from March 1998 to December 2000. Results: The identities of the 272 isolates tested with API Candida ...

  12. Antifungal drug susceptibility of Candida albicans | Bii | East African ...

    African Journals Online (AJOL)

    Objective: To determine the susceptibility of clinical isolates of Candida albicans and to establish the minimum inhibitory concentrations (MIC) to commonly used antifungal drugs. Design: Laboratory based experiment. Setting: Mbagathi District Hospital, Nairobi, Kenya. Subjects: Candida albicans isolated between 1998 ...

  13. Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Maxwel Adriano Abegg


    Full Text Available INTRODUCTION: The capacity to overcome the oxidative stress imposed by phagocytes seems to be critical for Candida species to cause invasive candidiasis. METHODS: To better characterize the oxidative stress response (OSR of 8 clinically relevant Candida sp., glutathione, a vital component of the intracellular redox balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB-glutathione disulfide (GSSG reductase reconversion method; the total antioxidant capacity (TAC was measured using a modified method based on the decolorization of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS*+. Both methods were used with cellular Candida sp. extracts treated or not with hydrogen peroxide (0.5 mM. RESULTS: Oxidative stress induced by hydrogen peroxide clearly reduced intracellular glutathione levels. This depletion was stronger in Candida albicans and the levels of glutathione in untreated cells were also higher in this species. The TAC demonstrated intra-specific variation. CONCLUSIONS: Glutathione levels did not correlate with the measured TAC values, despite this being the most important non-enzymatic intracellular antioxidant molecule. The results indicate that the isolated measurement of TAC does not give a clear picture of the ability of a given Candida sp. to respond to oxidative stress.

  14. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance (United States)

    Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.


    Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

  15. Clinical and Neurobiological Relevance of Current Animal Models of Autism Spectrum Disorders. (United States)

    Kim, Ki Chan; Gonzales, Edson Luck; Lázaro, María T; Choi, Chang Soon; Bahn, Geon Ho; Yoo, Hee Jeong; Shin, Chan Young


    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

  16. Design of a clinically relevant upper-limb exoskeleton robot for stroke patients with spasticity. (United States)

    Lee, Dong Jin; Bae, Sung Jin; Jang, Sung Ho; Chang, Pyung Hun


    The purpose of this research is to propose a design of a clinically relevant upper-limb (hand, wrist, and elbow) exoskeleton that meets the clinical requirements. At first, the proposed robot was designed to have sufficient torque for passive exercise therapy and spasticity measurement of post-stroke patients with spasticity (grade 3 or lower in Modified Ashworth Scale). Because the therapy of patients with high level spasticity could be laborious for therapists by increased muscle tone, and the patients tend not to get enough rehabilitation treatment. Secondly, this robot was designed to have user friendly features like as modularity, so that users have easy approach to assemble and disassemble for practical use. Thirdly, this robot system was designed to guarantee the safety for robot-aided passive training of patients with spasticity. As a result, we were able to see the usability of the robot system, even though it was a pilot test. This shows the possibility of measuring and classifying the spasticity.

  17. The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis. (United States)

    Tall, F; Dechomet, M; Riviere, S; Cottin, V; Ballot, E; Tiev, K P; Montin, R; Morin, C; Chantran, Y; Grange, C; Jullien, D; Ninet, J; Chretien, P; Cabane, J; Fabien, N; Johanet, C


    Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  18. Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer. (United States)

    Maughan, Benjamin L; Antonarakis, Emmanuel S


    Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

  19. Clinical Relevance of Sleep Duration: Results from a Cross-Sectional Analysis Using NHANES (United States)

    Cepeda, M. Soledad; Stang, Paul; Blacketer, Clair; Kent, Justine M.; Wittenberg, Gayle M.


    Study Objectives: To assess the clinical relevance of sleep duration, hours slept were compared by health status, presence of insomnia, and presence of depression, and the association of sleep duration with BMI and cardiovascular risk was quantified. Methods: Cross-sectional analysis of subjects in the US National Health and Nutrition Examination Surveys using adjusted linear and logistic regressions. Results: A total of 22,281 adults were included, 37% slept ≤ 6 hours, 36% were obese, and 45% reported cardiovascular conditions. Mean sleep duration was 6.87 hours. Better health was associated with more hours of sleep. Subjects with poor health reported sleeping 46 min, (95% CI −56.85 to −35.67) less than subjects with excellent health. Individuals with depression (vs. not depressed) reported 40 min less sleep, (95% CI −47.14 to −32.85). Individuals with insomnia (vs. without insomnia) reported 39 min less sleep, (95% CI −56.24 to −22.45). Duration of sleep was inversely related to BMI; for every additional hour of sleep, there was a decrease of 0.18 kg/m2 in BMI, (95% CI −0.30 to −0.06). The odds of reporting cardiovascular problems were 6.0% lower for every hour of sleep (odds ratio = 0.94, 95% CI [0.91 to 0.97]). Compared with subjects who slept ≤ 6 h, subjects who slept more had lower odds of reporting cardiovascular problems, with the exception of subjects ≥ 55 years old who slept ≥ 9 hours. Conclusions: Long sleep duration is associated with better health. The fewer the hours of sleep, the greater the BMI and reported cardiovascular disease. A difference of 30 minutes of sleep is associated with substantive impact on clinical well-being. Citation: Cepeda MS, Stang P, Blacketer C, Kent JM, Wittenberg GM. Clinical relevance of sleep duration: results from a cross-sectional analysis using NHANES. J Clin Sleep Med 2016;12(6):813–819. PMID:26951419

  20. The clinical relevance of outcomes used in late-onset Pompe disease: can we do better? (United States)

    Lachmann, Robin; Schoser, Benedikt


    Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. Clinical improvement was perceived by patients in 6 of the 10 studies. In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be

  1. Candida albicans and Candida parapsilosis induce different T-cell responses in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Toth, A.; Csonka, K.; Jacobs, C.; Vagvolgyi, C.; Nosanchuk, J.D.; Netea, M.G.; Gacser, A.


    Candida parapsilosis is the third most frequent cause of candidemia. Despite its clinical importance, little is known about the human immunological response to C. parapsilosis. In this study, we compared the cytokine responses evoked by Candida albicans and C. parapsilosis. C.

  2. Management of Candida biofilms: state of knowledge and new options for prevention and eradication. (United States)

    Bujdáková, Helena


    Biofilms formed by Candida species (spp.) on medical devices represent a potential health risk. The focus of current research is searching for new options for the treatment and prevention of biofilm-associated infections using different approaches including modern nanotechnology. This review summarizes current information concerning the most relevant resistance/tolerance mechanisms to conventional drugs and a role of additional factors contributing to these phenomena in Candida spp. (mostly Candida albicans). Additionally, it provides an information update in prevention and eradication of a Candida biofilm including experiences with 'lock' therapy, potential utilization of small molecules in biomedical applications, and perspectives of using photodynamic inactivation in the control of a Candida biofilm.

  3. White-opaque Switching in Different Mating Type-like Locus Gene Types of Clinical Candida albicans Isolates

    Directory of Open Access Journals (Sweden)

    Hou-Min Li


    Conclusions: From these analyses, there were comparatively more C. albicans strains classified into serotype B, and the frequency of opaque phase strains was significant in the clinical isolates from China. Genetic, phenotypic, or drug susceptibility patterns were not significantly different from previous studies. MTL a/α isolates could also undergo WO switching which facilitates their survival.

  4. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model. (United States)

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L


    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans. © 2014 American Heart Association, Inc.

  5. [Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas]. (United States)

    Brittinger, G; Bartels, H; Common, H; Dühmke, E; Engelhard, M; Fülle, H H; Gunzer, U; Gyenes, T; Heinz, R; König, E


    The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. (United States)

    Köhler-Forsberg, Ole; Sylvia, Louisa; Deckersbach, Thilo; Ostacher, Michael Joshua; McInnis, Melvin; Iosifescu, Dan; Bowden, Charles; McElroy, Susan; Calabrese, Joseph; Thase, Michael; Shelton, Richard Charles; Tohen, Mauricio; Kocsis, James; Friedman, Edward; Ketter, Terence; Nierenberg, Andrew Alan


    Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature

  7. Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data

    NARCIS (Netherlands)

    Winters, Bart; Montaner, Julio; Harrigan, P. Richard; Gazzard, Brian; Pozniak, Anton; Miller, Michael D.; Emery, Sean; van Leth, Frank; Robinson, Patrick; Baxter, John D.; Perez-Elias, Marie; Castor, Delivette; Hammer, Scott; Rinehart, Alex; Vermeiren, Hans; van Craenenbroeck, Elke; Bacheler, Lee


    BACKGROUND: Clinically relevant cutoffs are needed for the interpretation of HIV-1 phenotypic resistance estimates as predicted by "virtual" phenotype HIV resistance analysis. METHODS: Using a clinical data set containing 2596 treatment change episodes in 2217 patients in 8 clinical trials and 2

  8. [Phagocytosis and lysis of Candida albicans and Candida pseudotropicalis by polymorphonuclear neutrophils of Hansen's disease patients]. (United States)

    Fliess, E L; Comesaña, G; Carrara, R C; España, A


    The phagocytosis and lysis of Candida albicans and Candida pseudotropicalis by human neutrophils were examined in 43 hanseniasis patients (19 quiescent virchowians, 12 reactional virchowians and 12 tuberculoid patients) and 15 healthy subjects. The purpose of this study was to determine whether neutrophils from hanseniasis patients were altered in their enzyme systems myeloperoxidase-dependent (tested by lysin of Candida albicans) and myeloperoxidase-independent (tested by lysin of Candida pseudotropicalis). The results indicate that polymorphonuclear neutrophils of hanseniasis patients had a similar candidacidal activity that human normal neutrophils (p greater than 0.2) in their myeloperoxidase-dependent and myeloperoxidase-independent systems. The enzymatic system activity is also similar in all clinical forms of hanseniasis (p greater than 0.3).

  9. MFS transportome of the human pathogenic yeast Candida albicans. (United States)

    Gaur, Manisha; Puri, Nidhi; Manoharlal, Raman; Rai, Versha; Mukhopadhayay, Gauranga; Choudhury, Devapriya; Prasad, Rajendra


    The major facilitator superfamily (MFS) is one of the two largest superfamilies of membrane transporters present ubiquitously in bacteria, archaea, and eukarya and includes members that function as uniporters, symporters or antiporters. We report here the complete transportome of MFS proteins of a human pathogenic yeast Candida albicans. Computational analysis of C. albicans genome enabled us to identify 95 potential MFS proteins which clustered into 17 families using Saier's Transport Commission (TC) system. Among these SP, DHA1, DHA2 and ACS represented major families consisting of 22, 22, 9 and 16 members, respectively. Family designations in C. albicans were validated by subjecting Saccharomyces cerevisiae genome to TC system. Based on the published available genomics/proteomics data, 87 of the putative MFS genes of C. albicans were found to express either at mRNA or protein levels. We checked the expression of the remaining 8 genes by using RT-PCR and observed that they are not expressed under basal growth conditions implying that either these 8 genes are expressed under specific growth conditions or they may be candidates for pseudogenes. The in silico characterisation of MFS transporters in Candida albicans genome revealed a large complement of MFS transporters with most of them showing expression. Considering the clinical relevance of C. albicans and role of MFS members in antifungal resistance and nutrient transport, this analysis would pave way for identifying their physiological relevance.

  10. In vitro activity of micafungin against biofilms of Candida albicans, Candida glabrata, and Candida parapsilosis at different stages of maturation. (United States)

    Prażyńska, Małgorzata; Bogiel, Tomasz; Gospodarek-Komkowska, Eugenia


    Candida spp. is able to form a biofilm, which is considered resistant to the majority of antifungals used in medicine. The aim of this study was to evaluate the in vitro activity of micafungin against Candida spp. biofilms at different stages of their maturation (2, 6, and 24 h). We assessed the inhibitory effect of micafungin against 78 clinical isolates of Candida spp., growing as planktonic or sessile cells, by widely recommended broth microdilution method. The in vitro effect on sessile cells viability was evaluated by colorimetric reduction assay. All examined strains were susceptible or intermediate to micafungin when growing as planktonic cells. At the early stages of biofilm maturation, from 11 (39.3%) to 20 (100%), tested strains, depending on the species, exhibited sessile minimal inhibitory concentrations (SMICs) of micafungin at ≤ 2 mg/L. For 24-h-old Candida spp. biofilms, from 3 (10.7%) to 20 (100%) of the tested strains displayed SMICs of micafungin at ≤ 2 mg/L. Our findings confirm that micafungin exhibits high potential anti-Candida-biofilm activity. However, this effect does not comprise all Candida species and strains. All strains were susceptible or intermediate to micafungin when growing as planktonic cells, but for biofilms, micafungin displays species- and strain-specific activity. Paradoxical growth of C. albicans and C. parapsilosis was observed. Antifungal susceptibility testing of Candida spp. biofilms would be the best solution, but to date, no reference method is available. The strongest antibiofilm activity of micafungin is observed at early stages of biofilm formation. Possibly, micafungin could be considered as an effective agent for prevention of biofilm-associated candidiasis, especially catheter-related candidaemia.

  11. Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania.

    Directory of Open Access Journals (Sweden)

    Francis Mhimbira


    Full Text Available Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.Between November 2013 and October 2015, we enrolled adult (≥18 years sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB.A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972 were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597 and 25.9% (97/375 among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161, followed by hookworm (9.0%, 87 and Schistosoma mansoni (5.7%, 55. An infection with any helminth was not associated with TB (adjusted odds ratio (aOR 1.26, 95% confidence interval (CI: 0.88-1.80, p = 0.22, but S. mansoni infection was (aOR 2.15, 95% CI: 1.03-4.45, p = 0.040. Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38-5.26, p = 0.004 and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12-1.16, p = 0.088.S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB. Treatment of helminths should be considered in clinical management of

  12. [EDNOS is an eating disorder of clinical relevance, on a par with anorexia and bulimia nervosa]. (United States)

    Dingemans, A E; van Furth, E F


    The category 'eating disorder 'not otherwise specified'' (EDNOS) in DSM-IV is restricted to eating disorders of clinical severity that do not completely fulfil the criteria for anorexia and bulimia nervosa. The EDNOS category is, by definition, often regarded as a a residual category and in principle designed to incorporate a small group of patients with atypical characteristics. Health insurance companies argue that the treatment of patients diagnosed with EDNOS should not be treated in mental health institutions and therefore should not get their treatment costs reimbursed by the insurance companies. The most important argument of the insurance companies is that patients in the EDNOS category do not display serious psychiatric symptoms. The aim of this paper is to show that EDNOS is an eating disorder category of clinical relevance. The article provides a critical overview of literature on EDNOS which studies the prevalence, severity and course of the disorder. We also discuss to what extent the fifth version of dsm solves the problems relating to this residual category. We reviewed the literature. The classification given in DSM-IV is not an accurate reflection of clinical reality. Half of the patients presenting with an eating disorder and seeking treatment do meet the criteria for EDNOS. The duration and the severity of eating disorder psychopathology, the presence of comorbidity, the mortality, and the use of the mental health care services by individuals with an eating disorder appear to be very similar in EDNOS patients and in patients with anorexia and bulimia nervosa. Eating disorder classifications can be regarded as snapshots taken throughout the course of an illness. Over of the years patients can be afflicted with various subtypes of an eating disorder. DSM-5 places fewer patients in the EDNOS category that did DSM-IV. In the latest version of dsm, namely DSM-5, the number of patients with an eating disorder classified as EDNOS has declined. There

  13. The inter-examiner reliability of standardized manual palpation for the identification of clinically relevant myofascial triggerpoints

    DEFF Research Database (Denmark)

    Myburgh, Corrie; Lauridsen, Henrik Hein; Larsen, Anders Holsgaard

    A clinical diagnosis of Myofascial Pain Syndrome (MPS) requires manual palpation for the identification of at least one clinically relevant trigger point (TP). However, few comparable, high quality studies exist regarding the robustness of TP examination. Our aim was to determine the inter....../absence of clinically relevant TP(s) using clinician global assessment (GA). A random case mix of 81 female participants was examined, 14 being asymptomatic and the remainder suffering from neck/shoulder pain. Examiners received psychomotor training and video analysis feedback provided prior to and during the study...

  14. Evaluation of two matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems for the identification of Candida species. (United States)

    Lacroix, C; Gicquel, A; Sendid, B; Meyer, J; Accoceberry, I; François, N; Morio, F; Desoubeaux, G; Chandenier, J; Kauffmann-Lacroix, C; Hennequin, C; Guitard, J; Nassif, X; Bougnoux, M-E


    Candida spp. are responsible for severe infections in immunocompromised patients and those undergoing invasive procedures. The accurate identification of Candida species is important because emerging species can be associated with various antifungal susceptibility spectra. Conventional methods have been developed to identify the most common pathogens, but have often failed to identify uncommon species. Several studies have reported the efficiency of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of clinically relevant Candida species. In this study, we evaluated two commercially available MALDI-TOF systems, Andromas™ and Bruker Biotyper™, for Candida identification in routine diagnosis. For this purpose, we investigated 1383 Candida isolates prospectively collected in eight hospital laboratories during routine practice. MALDI-TOF MS results were compared with those obtained using conventional phenotypic methods. Analysis of rDNA gene sequences with internal transcribed regions or D1-D2 regions is considered the reference standard for identification. Both MALDI-TOF MS systems could accurately identify 98.3% of the isolates at the species level (1359/1383 for Andromas™; 1360/1383 for Bruker Biotyper™) vs. 96.5% for conventional techniques. Furthermore, whereas conventional methods failed to identify rare or emerging species, these were correctly identified by MALDI-TOF MS. Both MALDI-TOF MS systems are accurate and cost-effective alternatives to conventional methods for mycological identification of clinically relevant Candida species and should improve the diagnosis of fungal infections as well as patient management. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  15. Clinical relevance of [i]Corylus[/i] pollen in Poznań, western Poland

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    Łukasz Grewling


    Full Text Available Background. In Central Europe, hazel ([i]Corylus[/i] sp. pollen is considered to be an important aeroallergen in early spring. Objective. This study examines hazel pollen levels in Poznań, western Poland, and the clinical relevance of this aeroallergen in the city. Methods. [i]Corylus[/i] pollen data (1996–2010 were obtained by volumetric spore trap located near the centre of Poznań. Clinical data (2006–2010, i.e. skin prick test (SPT and allergen-specific IgE measurements (asIgE, were supplied by the Allergy Diseases Diagnostic Centre in Poznań. Results. Mean diurnal hazel pollen concentrations peaked around 14:00–16:00 when mean bi-hourly pollen concentrations were ~60 P m-3. Onset of the hazel pollen season varied up to 87 days annually, and was significantly (r=–0.647; p<0.01 related to mean maximum temperature during late December. SPT data revealed that ~11% of allergy patients had positive skin reactions to [i]Corylus[/i] pollen allergens, and most of these (94.4% reacted to pollen allergens from other members of the Betulaceae family – alder or birch. Of those sensitized, 53% suffered from atopic dermatitis. Of patients examined for serum asIgE, 26.0% had asIgE measurements in classes 5 and 6. Conclusions. Hazel pollen has a detrimental effect on the allergic population of Poznań, with more than half of those sensitised to hazel pollen allergens showing symptoms of atopic dermatitis. Hazel pollen concentrations reach levels recognized as being able to induce allergy symptoms, especially in the afternoon and early evening when many people are returning home from work. The cross-reactivity with other members of the Fagales order also increases the allergenic potential of hazel pollen.

  16. CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients. (United States)

    Maouia, A; Youssef, M; Leban, N; Ben Chibani, J; Helal, A N; Kassab, A


    Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least six weeks. Multifactorial origin is suggested such as oxidative stress. This latter may play a double role as a trigger and remnant agent. The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: desloratadine 5 mg/d on these different parameters. This study enrolled 30 CSU patients and same number of controls. We assessed the urticaria activity score (UAS), total antioxidant status (TAS), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), albumin, alpha1, alpha2, beta1 beta2, gamma globulins, c-reactive protein (CRP) and hematologic numeration. At baseline alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus controls (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were significantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CRP, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p < 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 d-antihistaminic treatment. Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients' remission was synergistic to CRP attenuation emphasizing CRP relevance for CSU clinical assessment.

  17. Antimicrobial drug resistance among clinically relevant bacterial isolates in sub-Saharan Africa: a systematic review. (United States)

    Leopold, Stije J; van Leth, Frank; Tarekegn, Hayalnesh; Schultsz, Constance


    Little is known about the prevalence of antimicrobial resistance (AMR) amongst bacterial pathogens in sub-Saharan Africa (sSA), despite calls for continent-wide surveillance to inform empirical treatment guidelines. We searched PubMed and additional databases for susceptibility data of key pathogens for surveillance, published between 1990 and 2013. Extracted data were standardized to a prevalence of resistance in populations of isolates and reported by clinical syndrome, microorganism, relevant antimicrobial drugs and region. We identified 2005 publications, of which 190 were analysed. Studies predominantly originated from east sSA (61%), were hospital based (60%), were from an urban setting (73%) and reported on isolates from patients with a febrile illness (42%). Quality procedures for susceptibility testing were described in resistance to chloramphenicol in Enterobacteriaceae, isolated from patients with a febrile illness, ranged between 31.0% and 94.2%, whilst MP of resistance to third-generation cephalosporins ranged between 0.0% and 46.5%. MP of resistance to nalidixic acid in Salmonella enterica Typhi ranged between 15.4% and 43.2%. The limited number of studies providing prevalence data on AMR in Gram-positive pathogens or in pathogens isolated from patients with a respiratory tract infection, meningitis, urinary tract infection or hospital-acquired infection suggested high prevalence of resistance to chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline and low prevalence to third-generation cephalosporins and fluoroquinolones. Our results indicate high prevalence of AMR in clinical bacterial isolates to antimicrobial drugs commonly used in sSA. Enhanced approaches for AMR surveillance are needed to support empirical therapy in sSA. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail:

  18. Clinical Relevance of Sleep Duration: Results from a Cross-Sectional Analysis Using NHANES. (United States)

    Cepeda, M Soledad; Stang, Paul; Blacketer, Clair; Kent, Justine M; Wittenberg, Gayle M


    To assess the clinical relevance of sleep duration, hours slept were compared by health status, presence of insomnia, and presence of depression, and the association of sleep duration with BMI and cardiovascular risk was quantified. Cross-sectional analysis of subjects in the US National Health and Nutrition Examination Surveys using adjusted linear and logistic regressions. A total of 22,281 adults were included, 37% slept ≤ 6 hours, 36% were obese, and 45% reported cardiovascular conditions. Mean sleep duration was 6.87 hours. Better health was associated with more hours of sleep. Subjects with poor health reported sleeping 46 min, (95% CI -56.85 to -35.67) less than subjects with excellent health. Individuals with depression (vs. not depressed) reported 40 min less sleep, (95% CI -47.14 to -32.85). Individuals with insomnia (vs. without insomnia) reported 39 min less sleep, (95% CI -56.24 to -22.45). Duration of sleep was inversely related to BMI; for every additional hour of sleep, there was a decrease of 0.18 kg/m(2) in BMI, (95% CI -0.30 to -0.06). The odds of reporting cardiovascular problems were 6.0% lower for every hour of sleep (odds ratio = 0.94, 95% CI [0.91 to 0.97]). Compared with subjects who slept ≤ 6 h, subjects who slept more had lower odds of reporting cardiovascular problems, with the exception of subjects ≥ 55 years old who slept ≥ 9 hours. Long sleep duration is associated with better health. The fewer the hours of sleep, the greater the BMI and reported cardiovascular disease. A difference of 30 minutes of sleep is associated with substantive impact on clinical well-being. © 2016 American Academy of Sleep Medicine.

  19. Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats. (United States)

    Turner, Ryan C; Naser, Zachary J; Logsdon, Aric F; DiPasquale, Kenneth H; Jackson, Garrett J; Robson, Matthew J; Gettens, Robert T T; Matsumoto, Rae R; Huber, Jason D; Rosen, Charles L


    Blast-induced traumatic brain injury represents a leading cause of injury in modern warfare with injury pathogenesis poorly understood. Preclinical models of blast injury remain poorly standardized across laboratories and the clinical relevance unclear based upon pulmonary injury scaling laws. Models capable of high peak overpressures and of short duration may better replicate clinical exposure when scaling principles are considered. In this work we demonstrate a tabletop shock tube model capable of high peak overpressures and of short duration. By varying the thickness of the polyester membrane, peak overpressure can be controlled. We used membranes with a thickness of 0.003, 0.005, 0.007, and 0.010 in to generate peak reflected overpressures of 31.47, 50.72, 72.05, and 90.10 PSI, respectively. Blast exposure was shown to decrease total activity and produce neural degeneration as indicated by fluoro-jade B staining. Similarly, blast exposure resulted in increased glial activation as indicated by an increase in the number of glial fibrillary acidic protein expressing astrocytes compared to control within the corpus callosum, the region of greatest apparent injury following blast exposure. Similar findings were observed with regard to activated microglia, some of which displayed phagocytic-like morphology within the corpus callosum following blast exposure, particularly with higher peak overpressures. Furthermore, hematoxylin and eosin staining showed the presence of red blood cells within the parenchyma and red, swollen neurons following blast injury. Exposure to blast with 90.10 PSI peak reflected overpressure resulted in immediate mortality associated with extensive intracranial bleeding. This work demonstrates one of the first examples of blast-induced brain injury in the rodent when exposed to a blast wave scaled from human exposure based on scaling principles derived from pulmonary injury lethality curves. © 2013.

  20. A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling. (United States)

    Eyckmans, J; Roberts, S J; Schrooten, J; Luyten, F P


    In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the 'osteoinductive program'. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.

  1. Clinical relevance of infections with zoonotic and human oral species of Campylobacter. (United States)

    Lee, Soomin; Lee, Jeeyeon; Ha, Jimyeong; Choi, Yukyung; Kim, Sejeong; Lee, Heeyoung; Yoon, Yohan; Choi, Kyoung-Hee


    Genus Campylobacter has been recognized as a causative bacterial agent of animal and human diseases. Human Campylobacter infections have caused more concern. Campylobacters can be classified into two groups in terms of their original host: zoonotic and human oral species. The major zoonotic species are Campylobacter jejuni and Campylobacter coli, which mostly reside in the intestines of avian species and are transmitted to humans via consumption of contaminated poultry products, thus causing human gastroenteritis and other diseases as sequelae. The other campylobacters, human oral species, include C. concisus, C. showae, C. gracilis, C. ureolyticus, C. curvus, and C. rectus. These species are isolated from the oral cavity, natural colonization site, but have potential clinical relevance in the periodontal region to varying extent. Two species, C. jejuni and C. coli, are believed to be mainly associated with intestinal diseases, but recent studies suggested that oral Campylobacter species also play a significant role in intestinal diseases. This review offers an outline of the two Campylobacter groups (zoonotic and human oral), their virulence traits, and the associated illnesses including gastroenteritis.

  2. Polypharmacy as a Risk Factor for Clinically Relevant Sarcopenia: Results From the Berlin Aging Study II. (United States)

    König, Maximilian; Spira, Dominik; Demuth, Ilja; Steinhagen-Thiessen, Elisabeth; Norman, Kristina


    Sarcopenia affects more than 10% of older adults. Next to age-associated physiologic changes, diseases like diabetes or inflammatory, neurological, malignant and endocrine disorders may contribute to the development of sarcopenia. Likewise, polypharmacy, i.e., multiple drug use, is common among older adults. Although the two conditions frequently co-occur, the association of polypharmacy with sarcopenia has not yet been examined. We investigated the association of polypharmacy and sarcopenia in a large cohort of community-dwelling older adults (60-84 years). Thousand five hundred and two participants from the Berlin Aging Study II were included. Polypharmacy was defined as concurrent use of 5 or more drugs (prescription and nonprescription). Body composition was assessed with dual-energy X-ray absorptiometry, and appendicular lean mass (ALM) was calculated as sum of the four limbs' lean mass. Sarcopenia was defined as low ALM-to-body mass index (BMI)-ratio using validated sex-specific cutoffs. Mean age was 68.7 ± 3.7 years, 50.7% were female. The median (interquartile range) number of drugs was 2 (1-4); 21.1% of subjects reported regular use of ≥5 drugs. Subjects with polypharmacy were more often sarcopenic according to the applied ALM/BMI-cutoffs (16.3% vs 6.9%, p sarcopenia (odds ratio = 2.24, 95% confidence interval [CI] = 1.33-3.75). Polypharmacy is associated with clinically relevant sarcopenia, as assessed by a low ALM/BMI.

  3. Analysis of clinically relevant mechanical and thermal characteristics of titanium foam spinal implants during drilling. (United States)

    Ito, Kiyoshi; Horiuchi, Tetsuyoshi; Murata, Takahiro; Hongo, Kazuhiro


    Although high biocompatibility promotes the use of titanium (Ti) alloy in spinal implants, this material shows high stiffness, which is an issue for removal by drilling. The recently developed, porous Ti foam implants, which have shown enhanced osteoformation, may overcome this flaw. Thus, this study aimed to compare the mechanical and thermal characteristics of Ti-foam (80 % porosity) and conventional Ti alloy (0 % porosity) implants drilled in clinically relevant conditions. Mechanical properties were analyzed by measuring axial and torque forces using a pressure sensor with a drill of 2.5-mm diameter at a rotation frequency of 20 Hz. Thermography was used to evaluate the heat generated by a diamond burr attached to a high-speed (80,000 rpm) drill. The torque and axial strengths of Ti foam (13.63 ± 1.43 and 82.60 ± 7.78 N, respectively) were significantly lower (P = 0.001) than those of Ti alloy (73.58 ± 13.60 and 850.72 ± 146.99 N, respectively). Furthermore, irrigation reduced the area of local heating for Ti foam to 56-82 % of that for Ti alloy, indicating lower thermal conductivity. These data suggest that the use of Ti foam implants may be advantageous in cases with a probability of implant drilling in the future.

  4. Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of the Fungal Genus Fusarium

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    Hafize Sav


    Full Text Available Clinically relevant members of the fungal genus, Fusarium, exhibit an extraordinary genetic diversity and cause a wide spectrum of infections in both healthy individuals and immunocompromised patients. Generally, Fusarium species are intrinsically resistant to all systemic antifungals. We investigated whether the presence or absence of the ability to produce biofilms across and within Fusarium species complexes is linked to higher resistance against antifungals. A collection of 41 Fusarium strains, obtained from 38 patients with superficial and systemic infections, and three infected crops, were tested, including 25 species within the Fusarium fujikuroi species complex, 14 from the Fusarium solani species complex (FSSC, one Fusarium dimerum species complex, and one Fusarium oxysporum species complex isolate. Of all isolates tested, only seven strains from two species of FSSC, five F. petroliphilum and two F. keratoplasticum strains, recovered from blood, nail scrapings, and nasal biopsy samples, could produce biofilms under the tested conditions. In the liquid culture tested, sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory concentrations (MICs for amphotericin B, voriconazole, and posaconazole, compared to their planktonic counterparts, indicating that the ability to form biofilm may significantly increase resistance. Collectively, this suggests that once a surface adherent biofilm has been established, therapies designed to kill planktonic cells of Fusarium are ineffective.

  5. NT-ProBNP levels in saliva and its clinical relevance to heart failure. (United States)

    Foo, Jared Yong Yang; Wan, Yunxia; Kostner, Karam; Arivalagan, Alicia; Atherton, John; Cooper-White, Justin; Dimeski, Goce; Punyadeera, Chamindie


    Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (pdiagnostic accuracy of 90.6%. We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

  6. Silica desiccant packets for storage and transport of Streptococcus pneumoniae and other clinically relevant species.

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    Casey L Pell

    Full Text Available Bacterial isolates are often transported between laboratories for research and diagnostic purposes. Silica desiccant packets (SDPs, which are inexpensive and do not require freezing, were evaluated for storage and recovery of bacterial isolates. Conditions such as inoculum size, swab type and temperature of storage were investigated using ten Streptococcus pneumoniae isolates. The optimized protocol was then tested using 49 additional S. pneumoniae isolates representing 40 serogroups. Overall, S. pneumoniae growth was considered satisfactory (>100 colony forming units for 98/109 (89.9% and 20/20 (100% swabs after 14 days at room temperature or 28 days at 4° C, respectively. Storage in SDPs did not impact on the ability of S. pneumoniae isolates to be subsequently serotyped. When the survival of nine other clinically relevant bacterial species was tested, seven were viable after 28 days at room temperature, the exceptions being Neisseria gonorrhoeae and Haemophilus influenzae. SDPs are suitable for transport and short-term storage of bacterial species including S. pneumoniae.

  7. Update on the Human Broad Tapeworm (Genus Diphyllobothrium), Including Clinical Relevance (United States)

    Scholz, Tomáš; Garcia, Hector H.; Kuchta, Roman; Wicht, Barbara


    Summary: Tapeworms (Cestoda) continue to be an important cause of morbidity in humans worldwide. Diphyllobothriosis, a human disease caused by tapeworms of the genus Diphyllobothrium, is the most important fish-borne zoonosis caused by a cestode parasite. Up to 20 million humans are estimated to be infected worldwide. Besides humans, definitive hosts of Diphyllobothrium include piscivorous birds and mammals, which represent a significant zoonotic reservoir. The second intermediate hosts include both freshwater and marine fish, especially anadromous species such as salmonids. The zoonosis occurs most commonly in countries where the consumption of raw or marinated fish is a frequent practice. Due to the increasing popularity of dishes utilizing uncooked fish, numerous cases of human infections have appeared recently, even in the most developed countries. As many as 14 valid species of Diphyllobothrium can cause human diphyllobothriosis, with D. latum and D. nihonkaiense being the most important pathogens. In this paper, all taxa from humans reported are reviewed, with brief information on their life history and their current distribution. Data on diagnostics, epidemiology, clinical relevance, and control of the disease are also summarized. The importance of reliable identification of human-infecting species with molecular tools (sequences of mitochondrial genes) as well as the necessity of epidemiological studies aimed at determining the sources of infections are pointed out. PMID:19136438

  8. Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance

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    Yunfei Zha


    Full Text Available Purpose. To investigate the reproducibility of aortic distensibility (D measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA. Methods. 54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1. and at the level of its maximal diameter (level 2. by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aortic D and anthropometric and biochemical parameters. Results. A mean distensibility of Dlevel  1.=(1.05±0.22×10-5  Pa-1 and Dlevel  2.=(0.49±0.18×10-5  Pa-1 was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2=0.68 to BMI, diastolic blood pressure, and AAA diameter. Conclusions. Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

  9. Comparative transcriptional analysis of clinically relevant heat stress response in Clostridium difficile strain 630.

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    Nigel G Ternan

    Full Text Available Clostridium difficile is considered to be one of the most important causes of health care-associated infections worldwide. In order to understand more fully the adaptive response of the organism to stressful conditions, we examined transcriptional changes resulting from a clinically relevant heat stress (41 °C versus 37 °C in C. difficile strain 630 and identified 341 differentially expressed genes encompassing multiple cellular functional categories. While the transcriptome was relatively resilient to the applied heat stress, we noted upregulation of classical heat shock genes including the groEL and dnaK operons in addition to other stress-responsive genes. Interestingly, the flagellin gene (fliC was downregulated, yet genes encoding the cell-wall associated flagellar components were upregulated suggesting that while motility may be reduced, adherence--to mucus or epithelial cells--could be enhanced during infection. We also observed that a number of phage associated genes were downregulated, as were genes associated with the conjugative transposon Tn5397 including a group II intron, thus highlighting a potential decrease in retromobility during heat stress. These data suggest that maintenance of lysogeny and genome wide stabilisation of mobile elements could be a global response to heat stress in this pathogen.

  10. Clinical relevancy and risks of potential drug-drug interactions in intensive therapy. (United States)

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava


    Evaluate the potential Drug-Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Prospective study (January-December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to "avoid concomitant use" or "suspension of medication", while 306 had as recommendation "continuous and adequate monitoring". The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management.

  11. Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects (United States)

    Schlumpf, Yolanda; Spinelli, Simona; Späti, Jakub; Brakowski, Janis; Quednow, Boris B.; Seifritz, Erich; Grosse Holtforth, Martin


    Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus–amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top–down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material. PMID:23887820

  12. Extracellular membrane vesicles in blood products-biology and clinical relevance

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    Emilija Krstova Krajnc


    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  13. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance (United States)

    Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João


    Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  14. Clinically relevant depressive symptoms in young stroke patients - results of the sifap1 study. (United States)

    Tanislav, Christian; Kropp, Peter; Grittner, Ulrike; Holzhausen, Martin; Fazekas, Franz; Jungehülsing, Gerhard Jan; Tatlisumak, Turgut; von Sarnowski, Bettina; Putaala, Jukka; Huber, Roman; Thijs, Vincent; Schmidt, Reinhold; Kaps, Manfred; Enzinger, Christian; Dichgans, Martin; Norrving, Bo; Rolfs, Arndt


    Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort. The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed. From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found. Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings. © 2015 S. Karger AG, Basel.

  15. 3D Culture as a Clinically Relevant Model for Personalized Medicine. (United States)

    Fong, Eliza Li Shan; Toh, Tan Boon; Yu, Hanry; Chow, Edward Kai-Hua


    Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.

  16. Antifungal activity of clinical Lactobacillus strains against Candida albicans biofilms: identification of potential probiotic candidates to prevent oral candidiasis. (United States)

    Rossoni, Rodnei Dennis; de Barros, Patrícia Pimentel; de Alvarenga, Janaina Araújo; Ribeiro, Felipe de Camargo; Velloso, Marisol Dos Santos; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos


    This study isolated Lactobacillus strains from caries-free subjects and evaluated the inhibitory effects directly on three strains of C. albicans, two clinical strains and one reference strain. Thirty Lactobacillus strains were isolated and evaluated for antimicrobial activity against in vitro C. albicans biofilms. L. paracasei 28.4, L. rhamnosus 5.2 and L. fermentum 20.4 isolates exhibited the most significant inhibitory activity against C. albicans. Co-incubation between these microorganisms resulted in deterrence of biofilm development and retardation of hyphal formation. The hindrance of biofilm development was characterized by the downregulated expression of C. albicans biofilm-specific genes (ALS3, HWP1, EFG1 and CPH1). L. paracasei 28.4, L. rhamnosus 5.2 and L. fermentum 20.4 demonstrated the ability to exert antifungal activity through the inhibition of C. albicans biofilms.

  17. Candida Arthritis: Analysis of 112 Pediatric and Adult Cases (United States)

    Gamaletsou, Maria N.; Rammaert, Blandine; Bueno, Marimelle A.; Sipsas, Nikolaos V.; Moriyama, Brad; Kontoyiannis, Dimitrios P.; Roilides, Emmanuel; Zeller, Valerie; Taj-Aldeen, Saad J.; Miller, Andy O.; Petraitiene, Ruta; Lortholary, Olivier; Walsh, Thomas J.


    Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy. PMID:26858961

  18. The inter-relationship of clinical parameters in congenital talipes equinovarus: relevance to pathological anatomy and clinical classification. (United States)

    Siddique, I; Choudry, Q; Paton, R W


    The clinical features that define congenital talipes equinovarus (CTEV) are the presence of four principal components, equinus, varus, adductus and cavus. Classification systems in CTEV often include a form of assessment of these components and also other concurrent clinical parameters which feature in the condition. Over a 14-year period from 1992 to 2006, 95 consecutive cases of CTEV were prospectively assessed and data recorded in order to investigate the relationships between the clinical parameters in CTEV and to compare these relationships with those that one would expect from our knowledge of the pathological anatomy and mechanics of the condition, relating these findings to the commonly used systems for classification. Ninety-five cases of CTEV had failed conservative treatment and had undergone surgical release. The mean age at surgical release and assessment was 9 months. Cluster analysis demonstrated that there were, broadly, two groups of patients. The first group was those patients with a greater equinus deformity (greater than 31°). This group had a greater adductus deformity and the presence of other parameters indicating increased severity (multiplanar stiffness with the presence of cavus and medial skin crease). The second group was those patients with a smaller equinus deformity (less than 31°) who were more heterogenous with regards to the other parameters. We analysed on a statistical basis the relevant aspects of the deformity in CTEV. We have demonstrated that there are certain parameters, namely, equinus and adductus, whose severity can reasonably predict the severity of other components of the deformity. With regards to hindfoot parameters, increased equinus is related to less sagittal plane reducibility and to stiff hindfoot varus (coronal plane stiffness). In terms of midfoot parameters, the degree of adductus is related to the presence of cavus deformity and the presence of a medial skin crease is associated with less reducibility of

  19. Conditions influencing the in vitro antifungal activity of lactoferrin combined with antimycotics against clinical isolates of Candida - Impact on the development of buccal preparations of lactoferrin

    NARCIS (Netherlands)

    Kuipers, ME; Beljaars, L; Van Beek, N; De Vries, HG; Heegsma, J; Van Den Berg, JJM; Meijer, DKF; Swart, PJ

    Lactoferrin, an iron-binding glycoprotein, is a potential agent for the treatment of oropharyngeal Candidiasis. The aim of the present study was to test the capability of lactoferrin, combined or not combined with conventional antifungal agents, to inhibit the growth of different Candida species

  20. Candida parapsilosis complex water isolates from a haemodialysis unit: biofilm production and in vitro evaluation of the use of clinical antifungals

    Directory of Open Access Journals (Sweden)

    Regina Helena Pires


    Full Text Available Candida parapsilosis, currently divided into three distinct species, proliferates in glucose-rich solutions and has been associated with infections resulting from the use of medical devices made of plastic, an environment common in dialysis centres. The aims of this study were (i to screen for Candida orthopsilosis and Candida metapsilosis (100 environmental isolates previously identified as C. parapsilosis, (ii to test the ability of these isolates to form biofilm and (iii to investigate the in vitro susceptibility of Candida spp biofilms to the antifungal agents, fluconazole (FLC and amphotericin B (AMB. Isolates were obtained from a hydraulic circuit collected from a haemodialysis unit. Based on molecular criteria, 47 strains were re-identified as C. orthopsilosis and 53 as C. parapsilosis. Analyses using a formazan salt reduction assay and total viable count, together with microscopy studies, revealed that 72 strains were able to form biofilm that was structurally similar, but with minor differences in morphology. A microtitre-based colorimetric assay used to test the susceptibility of fungal biofilms to AMB and FLC demonstrated that the C. parapsilosis complex displayed an increased resistance to these antifungal agents. The results from these analyses may provide a basis for implementing quality controls and monitoring to ensure the microbiological purity of dialysis water, including the presence of yeast.

  1. Comparison of a capillary gel electrophoresis-based multiplex PCR assay and ribosomal intergenic transcribed spacer-2 amplicon sequencing for identification of clinically important Candida species. (United States)

    Monstein, Hans-Jürg; Tärnberg, Maria; Persis, Shohreh; Johansson, Anders G


    The performance of a commercially available Seegene Seeplex STI Master Panel 3 multiplex PCR for Candida species identification was compared with an internal transcribed spacer 2 (ITS2) PCR assay. We found that the Seeplex assay was specific for identification of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. tropicalis and C. dubliniensis. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Paper-based microfluidic devices for analysis of clinically relevant analytes present in urine and saliva. (United States)

    Klasner, Scott A; Price, Alexander K; Hoeman, Kurt W; Wilson, Rashaun S; Bell, Kayla J; Culbertson, Christopher T


    We report the use of paper-based microfluidic devices fabricated from a novel polymer blend for the monitoring of urinary ketones, glucose, and salivary nitrite. Paper-based devices were fabricated via photolithography in less than 3 min and were immediately ready for use for these diagnostically relevant assays. Patterned channels on filter paper as small as 90 microm wide with barriers as narrow as 250 microm could be reliably patterned to permit and block fluid wicking, respectively. Colorimetric assays for ketones and nitrite were adapted from the dipstick format to this paper microfluidic chip for the quantification of acetoacetate in artificial urine, as well as nitrite in artificial saliva. Glucose assays were based on those previously demonstrated (Martinez et al., Angew Chem Int Ed 8:1318-1320, 1; Martinez et al., Anal Chem 10:3699-3707, 2; Martinez et al., Proc Nat Acad Sci USA 50:19606-19611, 3; Lu et al., Electrophoresis 9:1497-1500, 4; Abe et al., Anal Chem 18:6928-6934, 5). Reagents were spotted on the detection pad of the paper device and allowed to dry prior to spotting of samples. The ketone test was a two-step reaction requiring a derivitization step between the sample spotting pad and the detection pad, thus for the first time, confirming the ability of these paper devices to perform online multi-step chemical reactions. Following the spotting of the reagents and sample solution onto the paper device and subsequent drying, color images of the paper chips were recorded using a flatbed scanner, and images were converted to CMYK format in Adobe Photoshop CS4 where the intensity of the color change was quantified using the same software. The limit of detection (LOD) for acetoacetate in artificial urine was 0.5 mM, while the LOD for salivary nitrite was 5 microM, placing both of these analytes within the clinically relevant range for these assays. Calibration curves for urinary ketone (5 to 16 mM) and salivary nitrite (5 to 2,000 microM) were

  3. Predisposing factors endorsing Candida infections. (United States)

    Singh, Shweta; Fatima, Zeeshan; Hameed, Saif


    Candida albicans is an opportunistic human fungal pathogen which is involved in infections ranging from superficial, mucosal to systemic candidiasis. It is the fourth most leading cause of death in nosocomial infections. Candidal infections are increasing at an alarming rate due to poor clinical management in hospital settings, more use of antibiotics, increased drug resistance, immunosuppression and host-pathogen related factors. There are various predisposing factors which can be immunologic or non-immunologic in origin that make a person susceptible to such infections. This review article establishes the need to understand the various predisposing factors leading to Candidal infections and discusses them on a common platform.

  4. Locating relevant patient information in electronic health record data using representations of clinical concepts and database structures. (United States)

    Pan, Xuequn; Cimino, James J


    Clinicians and clinical researchers often seek information in electronic health records (EHRs) that are relevant to some concept of interest, such as a disease or finding. The heterogeneous nature of EHRs can complicate retrieval, risking incomplete results. We frame this problem as the presence of two gaps: 1) a gap between clinical concepts and their representations in EHR data and 2) a gap between data representations and their locations within EHR data structures. We bridge these gaps with a knowledge structure that comprises relationships among clinical concepts (including concepts of interest and concepts that may be instantiated in EHR data) and relationships between clinical concepts and the database structures. We make use of available knowledge resources to develop a reproducible, scalable process for creating a knowledge base that can support automated query expansion from a clinical concept to all relevant EHR data.

  5. Comparison of biomarker based Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and conventional methods in the identification of clinically relevant bacteria and yeast. (United States)

    Kassim, Ali; Pflüger, Valentin; Premji, Zul; Daubenberger, Claudia; Revathi, Gunturu


    MALDI-TOF MS is an analytical method that has recently become integral in the identification of microorganisms in clinical laboratories. It relies on databases that majorly employ pattern recognition or fingerprinting. Biomarker based databases have also been developed and there is optimism that these may be superior to pattern recognition based databases. This study compared the performance of ribosomal biomarker based MALDI-TOF MS and conventional methods in the identification of selected bacteria and yeast. The study was a cross sectional study identifying clinically relevant bacteria and yeast isolated from varied clinical specimens submitted to a clinical laboratory. The identification of bacteria using conventional Vitek 2™ automated system, serotyping and MALDI-TOF MS was performed as per standard operating procedures. Comparison of sensitivities were then carried out using Pearson Chi-Square test and p-value of bacteria and Gram positive bacteria to the species level. For the Gram positive bacteria, significant difference was observed in the identification of Coagulase negative Staphylococci (p = 0.000) and Enterococcus (p = 0.008). Significant difference was also observed between serotyping and MALDI-TOF MS (p = 0.005) and this was attributed to the lack of identification of Shigella species by MALDI-TOF MS. There was no significant difference observed in the identification of yeast however some species of Candida were unidentified by MALDI-TOF MS. Biomarker based MALDI-TOF MS had good performance in a clinical laboratory setting with high sensitivities in the identification of clinically relevant microorganisms.

  6. Characteristics, Clinical Relevance, and the Role of Echinocandins in Fungal-Bacterial Interactions. (United States)

    Arvanitis, Marios; Mylonakis, Eleftherios


    Fungal-bacterial interactions are common in the environment. The interactions between invasive fungi (eg, Candida species and Aspergillus species) and pathogenic bacteria can be particularly significant in the outcome of human infections. Study of these interactions in vivo using murine or invertebrate models, such as Caenorhabditis elegans or Galleria mellonella, has been very helpful in increasing our understanding of the pathogenesis of mixed infections and in identifying ways to use this between-kingdom interplay to our advantage. Based on their effect against fungal biofilms and their immunomodulatory properties, the newer class of antifungal agents, known as echinocandins, has the potential to be useful in polymicrobial infections and in high-risk complex infections such as ventilator-associated pneumonia or sepsis where colonization by fungi can lead to worse outcomes. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:

  7. Clinically Relevant Cut-off Points for the Diagnosis of Sarcopenia in Older Korean People. (United States)

    Choe, Yu-Ri; Joh, Ju-Youn; Kim, Yeon-Pyo


    The optimal criteria applied to older Korean people have not been defined. We aimed to define clinically relevant cut-off points for older Korean people and to compare the predictive validity with other definitions of sarcopenia. Nine hundred and sixteen older Koreans (≥65 years) were included in this cross-sectional observational study. We used conditional inference tree analysis to determine cut-off points for height-adjusted grip strength (GS) and appendicular skeletal muscle mass (ASM), for use in the diagnosis of sarcopenia. We then compared the Korean sarcopenia criteria with the Foundation for the National Institutes of Health and Asian Working Group for Sarcopenia criteria, using frailty, assessed with the Korean Frailty Index, as an outcome variable. For men, a residual GS (GSre) of ≤ 0.25 was defined as weak, and a residual ASM (ASMre) of ≤ 1.29 was defined as low. Corresponding cut-off points for women were a GSre of ≤ 0.17 and an ASMre of ≤ 0.69. GSre and ASMre values were adjusted for height. In logistic regression analysis with new cut-off points, the adjusted odds ratios for pre-frail or frail status in the sarcopenia group were 3.23 (95% confidence interval [CI] 1.33-7.83) for the men and 1.74 (95% CI 0.91-3.35) for the women. In receiver operating characteristic curve analysis, the unadjusted area under the curve for Korean sarcopenia criteria in men and women were 0.653 and 0.608, respectively (p sarcopenia in older Korean people.

  8. Clinical relevance of herpes simplex virus viremia in Intensive Care Unit patients. (United States)

    Lepiller, Q; Sueur, C; Solis, M; Barth, H; Glady, L; Lefebvre, F; Fafi-Kremer, S; Schneider, F; Stoll-Keller, F


    To determine the clinical relevance of herpes simplex virus (HSV) viremia episodes in critically ill adult patients. 1556 blood samples obtained for HSV PCR analysis in Intensive Care Unit (ICU) patients over 4 years were retrospectively analyzed, focusing on the comprehensive analysis of 88 HSV-viremic patients. HSV DNA was detected in 11.8% of samples from the ICU. HSV viral loads remained below 5×10(2) copies/ml in 68.2% of patients and exceeded 10(4) copies/ml in 7.9%. Episodes of HSV-viremia correlated with immunosuppressed status and mechanical ventilation in 79.5% and 65.9% of patients, respectively. Only a subset of patients exhibited HSV-related organ damage, including pneumonia and hepatitis (10.2% and 2.3%, respectively). The mortality rate in HSV-viremic patients was not significantly increased compared to the overall mortality rate in the ICU (27.3% vs. 22.9%, p = 0.33). Only patients with high HSV viral loads tended to have a higher, though non-significant, death rate (57.1%, p = 0.14). Our results suggest HSV viremia is common in ICU patients, potentially favored by immunocompromised status and mechanical ventilation. The global impact of HSV-viremia on mortality in the ICU was low. Quantifying HSV DNA may help identifying patients at-risk of severe HSV-induced symptoms. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  9. New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis

    Directory of Open Access Journals (Sweden)

    Dass Crispin R


    Full Text Available Abstract Background Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. Methods Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. Results JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5 resulted in lung micro-metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. Conclusions The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy.

  10. Pharmacokinetics of (synthetic) cannabinoids in pigs and their relevance for clinical and forensic toxicology. (United States)

    Schaefer, Nadine; Wojtyniak, Jan-Georg; Kettner, Mattias; Schlote, Julia; Laschke, Matthias W; Ewald, Andreas H; Lehr, Thorsten; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H


    Synthetic cannabinoids (SCs) are gaining increasing importance in clinical and forensic toxicology. They are consumed without any preclinical safety studies. Thus, controlled human pharmacokinetic (PK) studies are not allowed, although being relevant for interpretation of analytical results in cases of misuse or poisoning. As alternative, in a controlled animal experiment, six pigs per drug received a single intravenous dose of 200μg/kg BW each of Δ(9)-tetrahydrocannabinol (THC), 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210), or 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4). In addition, six pigs received a combination of the three drugs with the identical dose each. The drugs were determined in serum using LC-MS/MS. A population (pop) PK analysis revealed that a three-compartment model described best the PK data of all three cannabinoids. Central volumes of distribution were estimated at 0.29L/kg, 0.20L/kg, and 0.67L/kg for THC, JWH-210, and RCS-4, respectively. Clearances were 0.042L/min/kg, 0.048L/min/kg, and 0.093L/min/kg for THC, JWH-210, and RCS-4, respectively. The popPK THC pig model was upscaled to humans using allometric techniques. Comparison with published human data revealed that the concentration-time profiles could successfully be predicted. These findings indicate that pigs in conjunction with PK modeling technique may serve as a tool for prediction of human PK of SCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Clinical relevance of disturbances of sleep and vigilance in major depressive disorder: a review. (United States)

    Thase, Michael E; Murck, Harald; Post, Anke


    The primary objective of this article is to provide a concise review of the clinical relevance of sleep and vigilance in major depressive disorder. PubMed was reviewed (1990-2009) and English-language articles were identified using the key words sleep and depression and sleep and antidepressants. Secondary searches included articles cited in sources identified by the primary search. The narrative review provides brief descriptions of the normal physiology of sleep and changes associated with depression, as well as the impact of various treatments on these processes. Although it has long been known that sleep disturbances are an important characteristic of depression, relatively few studies have been conducted with the newer-generation antidepressants. Neither of the most widely used classes of antidepressants, the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, have particularly beneficial effects on sleep and, among the medications that reliably improve sleep efficiency, including mirtazapine and the tricyclic antidepressants, problems with daytime sedation can offset therapeutic benefit. Despite relatively widespread use, trazodone has not been demonstrated to be an effective and safe hypnotic in patients taking other antidepressants. For many patients, ongoing concomitant treatment with benzodiazepines and related drugs is the preferred option, again without convincing empirical support of longer-term efficacy. Among newer and investigational antidepressants, agomelatine shows promise with respect to both overall safety and effects on insomnia, although possible negative effects on liver function warrant further study. Sleep disturbances are a significant aspect of depressive syndromes, and relief of insomnia remains an important unmet need in antidepressant therapeutics. Development of a well-tolerated antidepressant medication that rapidly improves sleep maintenance without daytime sedation is a priority for drug

  12. Anatomical masking of pressure footprints based on the Oxford Foot Model: validation and clinical relevance. (United States)

    Giacomozzi, Claudia; Stebbins, Julie A


    Plantar pressure analysis is widely used in the assessment of foot function. In order to assess regional loading, a mask is applied to the footprint to sub-divide it into regions of interest (ROIs). The most common masking method is based on geometric features of the footprint (GM). Footprint masking based on anatomical landmarks of the foot has been implemented more recently, and involves the integration of a 3D motion capture system, plantar pressure measurement device, and a multi-segment foot model. However, thorough validation of anatomical masking (AM) using pathological footprints has not yet been presented. In the present study, an AM method based on the Oxford Foot Model (OFM) was compared to an equivalent GM. Pressure footprints from 20 young healthy subjects (HG) and 20 patients with clubfoot (CF) were anatomically divided into 5 ROIs using a subset of the OFM markers. The same foot regions were also identified by using a standard GM method. Comparisons of intra-subject coefficient of variation (CV) showed that the OFM-based AM was at least as reliable as the GM for all investigated pressure parameters in all foot regions. Clinical relevance of AM was investigated by comparing footprints from HG and CF groups. Contact time, maximum force, force-time integral and contact area proved to be sensitive parameters that were able to distinguish HG and CF groups, using both AM and GM methods However, the AM method revealed statistically significant differences between groups in 75% of measured variables, compared to 62% using a standard GM method, indicating that the AM method is more sensitive for revealing differences between groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Key differences between 13 KRAS mutation detection technologies and their relevance for clinical practice (United States)

    Sherwood, James L; Brown, Helen; Rettino, Alessandro; Schreieck, Amelie; Clark, Graeme; Claes, Bart; Agrawal, Bhuwnesh; Chaston, Ria; Kong, Benjamin S G; Choppa, Paul; Nygren, Anders O H; Deras, Ina L; Kohlmann, Alexander


    Introduction This study assessed KRAS mutation detection and functional characteristics across 13 distinct technologies and assays available in clinical practice, in a blinded manner. Methods Five distinct KRAS-mutant cell lines were used to study five clinically relevant KRAS mutations: p.G12C, p.G12D, p.G12V, p.G13D and p.Q61H. 50 cell line admixtures with low (50 and 100) mutant KRAS allele copies at 20%, 10%, 5%, 1% and 0.5% frequency were processed using quantitative PCR (qPCR) (n=3), matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) (n=2), next-generation sequencing (NGS) (n=6), digital PCR (n=1) and Sanger capillary sequencing (n=1) assays. Important performance differences were revealed, particularly assay sensitivity and turnaround time. Results Overall 406/728 data points across all 13 technologies were identified correctly. Successful genotyping of admixtures ranged from 0% (Sanger sequencing) to 100% (NGS). 5/6 NGS platforms reported similar allelic frequency for each sample. One NGS assay detected mutations down to a frequency of 0.5% and correctly identified all 56 samples (Oncomine Focus Assay, Thermo Fisher Scientific). One qPCR (Idylla, Biocartis) and MALDI-TOF (UltraSEEK, Agena Bioscience) assay identified 96% (all 100 copies and 23/25 at 50 copies input) and 92% (23/25 at 100 copies and 23/25 at 50 copies input) of samples, respectively. The digital PCR assay (KRAS PrimePCR ddPCR, Bio-Rad Laboratories) identified 60% (100 copies) and 52% (50 copies) of samples correctly. Turnaround time from sample to results ranged from ~2 hours (Idylla CE-IVD) to 2 days (TruSight Tumor 15 and Sentosa CE-IVD), to 2 weeks for certain NGS assays; the level of required expertise ranged from minimal (Idylla CE-IVD) to high for some technologies. Discussion This comprehensive parallel assessment used high molecular weight cell line DNA as a model system to address key questions for a laboratory when implementing routine

  14. NT-ProBNP levels in saliva and its clinical relevance to heart failure.

    Directory of Open Access Journals (Sweden)

    Jared Yong Yang Foo

    Full Text Available BACKGROUND: Current blood based diagnostic assays to detect heart failure (HF have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body's health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. METHODS: Saliva samples were collected from healthy volunteers (n = 40 who had no underlying heart conditions and HF patients (n = 45 at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R immunoassay was used to quantify NT-proBNP levels in saliva. RESULTS: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37 and the correlation was r(2 = 0.78 (p<0.01, y = 1.705× +1910.8. The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. CONCLUSION: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.

  15. Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction. (United States)

    Butler, Merlin G; McGuire, Austen; Manzardo, Ann M


    Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form. We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions. By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution

  16. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. (United States)

    Nakamura, Koji; Sawada, Kenjiro; Yoshimura, Akihiko; Kinose, Yasuto; Nakatsuka, Erika; Kimura, Tadashi


    Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to

  17. Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia. (United States)

    Yamada, S; Hongo, T; Okada, S; Watanabe, C; Fujii, Y; Ohzeki, T


    To determine the clinical relevance of in vitro drug chemoresistance in childhood acute myeloid leukemia, we used an MTT assay to test leukemic cells from 132 newly diagnosed children. Patients were diagnosed according to the French-American-British (FAB) classification as follows: M0 (n = 12), M1 (n = 16), M2 (n = 53), M4 (n = 17), M5 (n = 19) and M7 (n = 15). The results revealed that, compared to leukemic cells from complete-responders (n = 107), those from non-responders who failed induction therapy (n = 17) were 1.4 to 5.0 times more resistant in vitro to cytarabine (P = 0.005), melphalan (P = 0.003), etoposide (P = 0.011), L-asparaginase (P = 0.017), aclarubicin (P = 0.026) and dexamethasone (P = 0.039). For seven other drugs tested, the median lethal dose of 70% and leukemic cell survival of non-responders were higher than those of complete-responders, but the difference was not statistically significant. We sought correlations between FAB subtypes and in vitro drug resistance. Leukemias of the FAB M4 and M5 subtype were more sensitive to L-asparaginase (P = 0.01, P = 0.0036) than those of the FAB M2 subtype. FAB M5 leukemia was more sensitive to etoposide than were the FAB M2, M4 and M7 subtypes (P = 0.001, P = 0.034, P = 0.023, respectively). By contrast, FAB M5 leukemia was significantly more resistant to prednisolone and dexamethasone than were the FAB M0, M1, M2, M4 and M7 subtypes. We sought correlations between in vitro drug resistance and long-term clinical outcome, but found no associations in this case. These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy. Selecting an appropriate anti-cancer drug according to the FAB classification together with drug sensitivity testing may contribute to improved prognoses in childhood acute myeloid leukemia.

  18. Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong In Vitro Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds. (United States)

    Schell, W A; Jones, A M; Garvey, E P; Hoekstra, W J; Schotzinger, R J; Alexander, B D


    The in vitro activities of fungal CYP51 inhibitors VT-1161 and VT-1129 were determined for Candida glabrata (n = 34) and C. krusei (n = 50). C. glabrata isolates were screened for FKS gene mutations. All isolates were resistant clinically and/or in vitro to at least one standard antifungal compound. VT-1161 and VT-1129 MICs for all isolates were at least 5-fold below achievable human plasma levels for VT-1161. VT-1161 and VT-1129 are promising for the treatment of resistant C. glabrata and C. krusei infections. Copyright © 2017 American Society for Microbiology.

  19. [Comparison of microdilution and disk diffusion methods for the detection of fluconazole and voriconazole susceptibility against clinical Candida glabrata isolates and determination of changing susceptibility with new CLSI breakpoints]. (United States)

    Hazırolan, Gülşen; Sarıbaş, Zeynep; Arıkan Akdağlı, Sevtap


    Candida albicans is the most frequently isolated species as the causative agent of Candida infections. However, in recent years, the isolation rate of non-albicans Candida species have increased. In many centers, Candida glabrata is one of the commonly isolated non-albicans species of C.glabrata infections which are difficult-to-treat due to decreased susceptibility to fluconazole and cross-resistance to other azoles. The aims of this study were to determine the in vitro susceptibility profiles of clinical C.glabrata isolates against fluconazole and voriconazole by microdilution and disk diffusion methods and to evaluate the results with both the previous (CLSI) and current species-specific CLSI (Clinical and Laboratory Standards Institute) clinical breakpoints. A total of 70 C.glabrata strains isolated from clinical samples were included in the study. The identification of the isolates was performed by morphologic examination on cornmeal Tween 80 agar and assimilation profiles obtained by using ID32C (BioMérieux, France). Broth microdilution and disk diffusion methods were performed according to CLSI M27-A3 and CLSI M44-A2 documents, respectively. The results were evaluated according to CLSI M27-A3 and M44-A2 documents and new vs. species-specific CLSI breakpoints. By using both previous and new CLSI breakpoints, broth microdilution test results showed that voriconazole has greater in vitro activity than fluconazole against C.glabrata isolates. For the two drugs tested, very major error was not observed with disk diffusion method when microdilution method was considered as the reference method. Since "susceptible" category no more exists for fluconazole vs. C.glabrata, the isolates that were interpreted as susceptible by previous breakpoints were evaluated as susceptible-dose dependent by current CLSI breakpoints. Since species-specific breakpoints remain yet undetermined for voriconazole, comparative analysis was not possible for this agent. The results obtained

  20. The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers | Office of Cancer Genomics (United States)

    Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions.

  1. Candida infection of the skin (United States)

    ... this page: // Candida infection of the skin To use the sharing features on this page, please enable JavaScript. Candida infection of the skin is a yeast infection ...

  2. In Vitro Antifungal Susceptibility of Oral Candida Isolates from Patients Suffering from Caries and Chronic Periodontitis. (United States)

    De-la-Torre, Janire; Ortiz-Samperio, María Esther; Marcos-Arias, Cristina; Marichalar-Mendia, Xabier; Eraso, Elena; Echebarria-Goicouria, María Ángeles; Aguirre-Urizar, José Manuel; Quindós, Guillermo


    Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.

  3. Overcoming the heterologous bias: An in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Puri, Nidhi; Manoharlal, Raman; Sharma, Monika [Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067 (India); Sanglard, Dominique [Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne (Switzerland); Prasad, Rajendra, E-mail: [Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067 (India)


    Research highlights: {yields} First report to demonstrate an in vivo expression system of an ABC multidrug transporter CgCdr1p of C. glabrata. {yields} First report on the structure and functional characterization of CgCdr1p. {yields} Functional conservation of divergent but typical residues of CgCdr1p. {yields} CgCdr1p elicits promiscuity towards substrates and has a large drug binding pocket with overlapping specificities. -- Abstract: We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplished by tagging a green fluorescent protein (GFP) downstream of ORF of CgCDR1 and integrating the resultant fusion protein at its native chromosomal locus in AS and AR backgrounds. The characterization confirmed that in comparison to AS isolate, CgCdr1p-GFP was over-expressed in AR isolates due to its hyperactive native promoter and the GFP tag did not affect its functionality in either construct. We observed that in addition to Rhodamine 6 G (R6G) and Fluconazole (FLC), a recently identified fluorescent substrate of multidrug transporters Nile Red (NR) could also be expelled by CgCdr1p. Competition assays with these substrates revealed the presence of overlapping multiple drug binding sites in CgCdr1p. Point mutations employing site directed mutagenesis confirmed that the role played by unique amino acid residues critical to ATP catalysis and localization of ABC drug transporter proteins are well conserved in C. glabrata as in other yeasts. This study demonstrates a first in vivo novel system where over-expression of GFP tagged MDR transporter protein can be driven by its own hyperactive promoter of AR isolates. Taken together, this in vivo system can be exploited for the structure and functional analysis of CgCdr1p and similar proteins wherein the arte-factual concerns

  4. [Urinary tract infection by Candida species]. (United States)

    González-Pedraza Avilés, Alberto; Luís Hernández, Rosalina; Luna Avila, Jesús; Dávila Mendoza, Rocío; Ortiz Zaragoza, Catalina


    To determine the frequency and characteristics of urinary tract infection (UTI) by Candida in diabetic patients (with and without symptoms) and to compare them with non-diabetic patients (with and without symptoms). Longitudinal, descriptive, and observational study. Study conducted at the "Dr Ignacio Chavez" Clinic of family medicine, ISSSTE: Mexico. There were 2 kinds of patients; 1 with diabetes mellitus diagnosis (DM) with and without clinical picture of probable urinary tract infection (UTI), and 1 without DM and with and without clinical picture of probable UTI. A urine culture and a confidential questionnaire were administered to find the presence of urinary symptoms and likely risk factors associated with the infection. To associate these risks, the chi2 statistical method was used, with significance at 95% and Fisher's Exact Test for small frequencies, using the EpiInfo V.6.0 program. Two hundred thirty seven patients between 28 and 82 years old were included. The prevalence of urinary infection by Candida was 5.1%, but only 33% of these had C albicans. There was no association between candidiasis and factors like age, sex, or presence of DM, but it was related to previous treatments, previous UTI and the evolution time of DM. The conscious search by both doctor and laboratory for Candida micro-organisms as factors causing UTI is important. This is especially so in those patients with factors of risk that may condition Candida's presence.

  5. Thrush and Other Candida Infections (United States)

    ... Text Size Email Print Share Thrush and Other Candida Infections Page Content Article Body The fungus Candida is normally found on and in the body ... tract and genital area. Most of the time, Candida does not cause any symptoms. When these organisms ...

  6. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. (United States)

    Wiebe, Natasha; Padwal, Raj; Field, Catherine; Marks, Seth; Jacobs, Rene; Tonelli, Marcello


    The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role of hypocaloric sweeteners in a wider

  7. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes

    Directory of Open Access Journals (Sweden)

    Wiebe Natasha


    Full Text Available Abstract Background The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. Methods We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. Results Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34 compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806. One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively. No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. Conclusions Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are

  8. Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant. (United States)

    Steenwijk, Martijn D; Geurts, Jeroen J G; Daams, Marita; Tijms, Betty M; Wink, Alle Meije; Balk, Lisanne J; Tewarie, Prejaas K; Uitdehaag, Bernard M J; Barkhof, Frederik; Vrenken, Hugo; Pouwels, Petra J W


    %). Several cortical atrophy patterns relevant for multiple sclerosis were found. This suggests that cortical atrophy in multiple sclerosis occurs largely in a non-random manner and develops (at least partly) according to distinct anatomical patterns. In addition, these cortical atrophy patterns showed stronger associations with clinical (especially cognitive) dysfunction than global cortical atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:

  9. SU-F-T-345: Quasi-Dead Beams: Clinical Relevance and Implications for Automatic Planning

    Energy Technology Data Exchange (ETDEWEB)

    Price, R; Veltchev, I; Lin, T; Gleason, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)


    Purpose: Beam direction selection for fixed-beam IMRT planning is typically a manual process. Severe dose-volume limits on critical structures in the thorax often result in atypical selection of beam directions as compared to other body sites. This work demonstrates the potential consequences as well as clinical relevance. Methods: 21 thoracic cases treated with 5–7 beam directions, 6 cases including non-coplanar arrangements, with fractional doses of 150–411cGy were analyzed. Endpoints included per-beam modulation scaling factor (MSF), variation from equal weighting, and delivery QA passing rate. Results: During analysis of patient-specific delivery QA a sub-standard passing rate was found for a single 5-field plan (90.48% of pixels evaluated passing 3% dose, 3mm DTA). During investigation it was found that a single beam demonstrated a MSF of 34.7 and contributed only 2.7% to the mean dose of the target. In addition, the variation from equal weighting for this beam was 17.3% absolute resulting in another beam with a MSF of 4.6 contributing 41.9% to the mean dose to the target; a variation of 21.9% from equal weighting. The average MSF for the remaining 20 cases was 4.0 (SD 1.8) with an average absolute deviation of 2.8% from equal weighting (SD 3.1%). Conclusion: Optimization in commercial treatment planning systems typically results in relatively equally weighted beams. Extreme variation from this can result in excessively high MSFs (very small segments) and potential decreases in agreement between planned and delivered dose distributions. In addition, the resultant beam may contribute minimal dose to the target (quasi-dead beam); a byproduct being increased treatment time and associated localization uncertainties. Potential ramifications exist for automatic planning algorithms should they allow for user-defined beam directions. Additionally, these quasi-dead beams may be embedded in the libraries for model-based systems potentially resulting in inefficient

  10. Rapid, accurate, and comparative differentiation of clinically and industrially relevant microorganisms via multiple vibrational spectroscopic fingerprinting. (United States)

    Muhamadali, Howbeer; Subaihi, Abdu; Mohammadtaheri, Mahsa; Xu, Yun; Ellis, David I; Ramanathan, Rajesh; Bansal, Vipul; Goodacre, Royston


    Despite the fact that various microorganisms (e.g., bacteria, fungi, viruses, etc.) have been linked with infectious diseases, their crucial role towards sustaining life on Earth is undeniable. The huge biodiversity, combined with the wide range of biochemical capabilities of these organisms, have always been the driving force behind their large number of current, and, as of yet, undiscovered future applications. The presence of such diversity could be said to expedite the need for the development of rapid, accurate and sensitive techniques which allow for the detection, differentiation, identification and classification of such organisms. In this study, we employed Fourier transform infrared (FT-IR), Raman, and surface enhanced Raman scattering (SERS) spectroscopies, as molecular whole-organism fingerprinting techniques, combined with multivariate statistical analysis approaches for the classification of a range of industrial, environmental or clinically relevant bacteria (P. aeruginosa, P. putida, E. coli, E. faecium, S. lividans, B. subtilis, B. cereus) and yeast (S. cerevisiae). Principal components-discriminant function analysis (PC-DFA) scores plots of the spectral data collected from all three techniques allowed for the clear differentiation of all the samples down to sub-species level. The partial least squares-discriminant analysis (PLS-DA) models generated using the SERS spectral data displayed lower accuracy (74.9%) when compared to those obtained from conventional Raman (97.8%) and FT-IR (96.2%) analyses. In addition, whilst background fluorescence was detected in Raman spectra for S. cerevisiae, this fluorescence was quenched when applying SERS to the same species, and conversely SERS appeared to introduce strong fluorescence when analysing P. putida. It is also worth noting that FT-IR analysis provided spectral data of high quality and reproducibility for the whole sample set, suggesting its applicability to a wider range of samples, and perhaps the

  11. Cost-effective multiplexing before capture allows screening of 25 000 clinically relevant SNPs in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Dalgaard, M. D.; Borst, L.


    designed a cost-effective, high-throughput capture assay of â¼25â000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows...

  12. Selecting relevant and feasible measurement instruments for the revised Dutch clinical practice guideline for physical therapy in patients after stroke

    NARCIS (Netherlands)

    Otterman, N.; Veerbeek, J.; Schiemanck, S.; Wees, P.J. van der; Nollet, F.; Kwakkel, G.


    PURPOSE: To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. METHODS: In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability

  13. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    NARCIS (Netherlands)

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.


    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and

  14. Comparative Evaluation of Etest, EUCAST, and CLSI Methods for Amphotericin B, Voriconazole, and Posaconazole against Clinically Relevant Fusarium Species

    NARCIS (Netherlands)

    Al-Hatmi, A.M.; Normand, A.C.; Ranque, S.; Piarroux, R.; Hoog, G.S. de; Meletiadis, J.; Meis, J.F.G.M.


    We compared EUCAST and CLSI methods versus Etest for antifungal susceptibility testing of 20 clinically relevant Fusarium species against amphotericin B, posaconazole, and voriconazole. The median Etest amphotericin B and posaconazole MICs were 1 dilution higher than the median EUCAST and the CLSI

  15. Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention

    DEFF Research Database (Denmark)

    Henriksen, N A; Meyhoff, C S; Wetterslev, J


    hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant...

  16. Time-driven activity-based costing in an outpatient clinic environment: development, relevance and managerial impact. (United States)

    Demeere, Nathalie; Stouthuysen, Kristof; Roodhooft, Filip


    Healthcare managers are continuously urged to provide better patient services at a lower cost. To cope with these cost pressures, healthcare management needs to improve its understanding of the relevant cost drivers. Through a case study, we show how to perform a time-driven activity-based costing of five outpatient clinic's departments and provide evidence of the benefits of such an analysis.

  17. Bottom–up protein identifications from microliter quantities of individual human tear samples. Important steps towards clinical relevance.

    Directory of Open Access Journals (Sweden)

    Peter Raus


    With 375 confidently identified proteins in the healthy adult tear, the obtained results are comprehensive and in large agreement with previously published observations on pooled samples of multiple patients. We conclude that, to a limited extent, bottom–up tear protein identifications from individual patients may have clinical relevance.

  18. Reporting the results of meta-analyses: a plea for incorporating clinical relevance referring to an example. (United States)

    Bartels, Ronald H M A; Donk, Roland D; Verhagen, Wim I M; Hosman, Allard J F; Verbeek, André L M


    The results of meta-analyses are frequently reported, but understanding and interpreting them is difficult for both clinicians and patients. Statistical significances are presented without referring to values that imply clinical relevance. This study aimed to use the minimal clinically important difference (MCID) to rate the clinical relevance of a meta-analysis. This study is a review of the literature. This study is a review of meta-analyses relating to a specific topic, clinical results of cervical arthroplasty. The outcome measure used in the study was the MCID. We performed an extensive literature search of a series of meta-analyses evaluating a similar subject as an example. We searched in Pubmed and Embase through August 9, 2016, and found articles concerning meta-analyses of the clinical outcome of cervical arthroplasty compared with that of anterior cervical discectomy with fusion in cases of cervical degenerative disease. We evaluated the analyses for statistical significance and their relation to MCID. MCID was defined based on results in similar patient groups and a similar disease entity reported in the literature. We identified 21 meta-analyses, only one of which referred to MCID. However, the researchers used an inappropriate measurement scale and, therefore, an incorrect MCID. The majority of the conclusions were based on statistical results without mentioning clinical relevance. The majority of the articles we reviewed drew conclusions based on statistical differences instead of clinical relevance. We recommend introducing the concept of MCID while reporting the results of a meta-analysis, as well as mentioning the explicit scale of the analyzed measurement. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Candida auris: emergence and epidemiology of a highly pathogenic yeast

    Directory of Open Access Journals (Sweden)

    Paula Slomp Santos


    Full Text Available Candida auris is a multidrug-resistant emerging yeast, which was responsible for healthcare-associated infection outbreaks, and was cataloged as a new species in 2009, after being isolated from a patient’s ear canal secretion in Japan. Since the notification of this first occurrence, numerous cases have been reported throughout the world, including Brazil. C. auris affects mainly inpatients, patients in intensive care units, exposed to broad-spectrum antifungal medications and who make use of vascular catheters. Currently, this yeast is one of the main responsible for invasive infections in hospitals and has been cause of concern by authorities and organs due to its rapid dissemination and difficult treatment caused by its low susceptibility to antifungal agents traditionally used in clinical practice. As a contributor to the severity of infections associated with C. auris, the transmission mechanism is still unknown, which implies in a lack of control of the microorganism and high mortality rates. Thus, this literature review presents relevant information in order to alert the importance of C. auris as an etiological agent of systemic infections, as well as its epidemiology and the real challenges of the treatment. Keywords: Candida auris; candidiasis; candidemia; multidrug-resistance; biofilm; epidemiology; diagnosis

  20. Prospective evaluation of the chromogenic medium CandiSelect 4 for differentiation and presumptive identification of non-Candida albicans Candida species. (United States)

    Zhao, Liang; de Hoog, G Sybren; Cornelissen, Akke; Lyu, Qian; Mou, Lili; Liu, Taohua; Cao, Yu; Vatanshenassan, Mansoureh; Kang, Yingqian


    Rapid identification of pathogenic yeasts is a crucial step in timely and appropriate antifungal therapy. For diagnostics in the clinical laboratory, simplified alternatives to barcoding are needed. CandiSelect 4 (CS4) medium, a chromogenic medium for isolation of clinical yeasts, allows routine recognition of Candida albicans and presumptive identification of Candida tropicalis, Candida glabrata, and Candida krusei. We evaluated an extension of this method with 46 non-Candida albicans Candida (NCAC) and 7 Malassezia species. The medium supported growth of all species tested and a wide diversity of cultural types were observed. Colony colours were in violet, turquoise (including green and blue), or white tinges. Eight NCAC species produced violet pigmentation similar to that of C. albicans. Most NCAC species, including C. glabrata and C. tropicalis were distributed in the turquoise group. Malassezia species were invariably blue. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  1. The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults

    DEFF Research Database (Denmark)

    Osterballe, M.; Hansen, T.K.; Mørtz, Charlotte G


    BACKGROUND: Previous studies have described cross-reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults with and without symptoms in the pollen...... season. OBJECTIVE: The aim of this study was to estimate the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults and to examine the diagnostic value of skin-prick test (SPT), histamine release and specific IgE compared with the outcome...... of oral challenge. METHODS: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross-reactivity with pollen-related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. RESULTS...

  2. Importance of Candida-bacterial polymicrobial biofilms in disease. (United States)

    Harriott, Melphine M; Noverr, Mairi C


    Candida albicans is the most prevalent human fungal pathogen, with an ability to inhabit diverse host niches and cause disease in both immunocompetent and immunocompromised individuals. C. albicans also readily forms biofilms on indwelling medical devices and mucosal tissues, which serve as an infectious reservoir that is difficult to eradicate, and can lead to lethal systemic infections. Biofilm formation occurs within a complex milieu of host factors and other members of the human microbiota. Polymicrobial interactions will probably dictate the cellular and biochemical composition of the biofilm, as well as influence clinically relevant outcomes, such as drug and host resistance and virulence. In this manuscript, we review C. albicans infections in the context of in vivo polymicrobial biofilms and implications for pathogenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Natural language processing of radiology reports for the detection of thromboembolic diseases and clinically relevant incidental findings. (United States)

    Pham, Anne-Dominique; Névéol, Aurélie; Lavergne, Thomas; Yasunaga, Daisuke; Clément, Olivier; Meyer, Guy; Morello, Rémy; Burgun, Anita


    Natural Language Processing (NLP) has been shown effective to analyze the content of radiology reports and identify diagnosis or patient characteristics. We evaluate the combination of NLP and machine learning to detect thromboembolic disease diagnosis and incidental clinically relevant findings from angiography and venography reports written in French. We model thromboembolic diagnosis and incidental findings as a set of concepts, modalities and relations between concepts that can be used as features by a supervised machine learning algorithm. A corpus of 573 radiology reports was de-identified and manually annotated with the support of NLP tools by a physician for relevant concepts, modalities and relations. A machine learning classifier was trained on the dataset interpreted by a physician for diagnosis of deep-vein thrombosis, pulmonary embolism and clinically relevant incidental findings. Decision models accounted for the imbalanced nature of the data and exploited the structure of the reports. The best model achieved an F measure of 0.98 for pulmonary embolism identification, 1.00 for deep vein thrombosis, and 0.80 for incidental clinically relevant findings. The use of concepts, modalities and relations improved performances in all cases. This study demonstrates the benefits of developing an automated method to identify medical concepts, modality and relations from radiology reports in French. An end-to-end automatic system for annotation and classification which could be applied to other radiology reports databases would be valuable for epidemiological surveillance, performance monitoring, and accreditation in French hospitals.

  4. The Intestinal Microbiome in Infectious Diseases: The Clinical Relevance of a Rapidly Emerging Field

    NARCIS (Netherlands)

    Harris, Vanessa C.; Haak, Bastiaan W.; Boele van Hensbroek, Michaël; Wiersinga, Willem J.


    The field of infectious disease is undergoing a paradigm shift as the intestinal microbiome is becoming understood. The aim of this review is to inform infectious disease physicians of the potential relevance of the intestinal microbiome to their practice. We searched Medline using both index and

  5. Assessment and clinical relevance of non-fasting and postprandial triglycerides

    DEFF Research Database (Denmark)

    Kolovou, Genovefa D; Mikhailidis, Dimitri P; Kovar, Jan


    An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non...

  6. Multidrug-Resistant Candida

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Patterson, Thomas F


    Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistan...

  7. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation


    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar


    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  8. Evaluation of chromogenic media and seminested PCR in the identification of Candida species (United States)

    Daef, Enas; Moharram, Ahmed; Eldin, Salwa Seif; Elsherbiny, Nahla; Mohammed, Mona


    Identification of Candida cultured from various clinical specimens to the species level is increasingly necessary for clinical laboratories. Although sn PCR identifies the species within hours but its cost-effectiveness is to be considered. So there is always a need for media which help in the isolation and identification at the species level. The study aimed to evaluate the performance of different chromogenic media and to compare the effectiveness of the traditional phenotypic methods vs. seminested polymerase chain reaction (sn PCR) for identification of Candida species. One hundred and twenty seven Candida strains isolated from various clinical specimens were identified by conventional methods, four different chromogenic media and sn PCR. HiCrome Candida Differential and CHROMagar Candida media showed comparably high sensitivities and specificities in the identification of C. albicans, C. tropicalis, C. glabrata and C. krusei. CHROMagar Candida had an extra advantage of identifying all C. parapsilosis isolates. CHROMagar-Pal’s medium identified C. albicans, C. tropicalis and C. krusei with high sensitivities and specificities, but couldn’t identify C. glabrata or C. parapsilosis. It was the only medium that identified C. dubliniensis with a sensitivity and specificity of 100%. Biggy agar showed the least sensitivities and specificities. The overall concordance of the snPCR compared to the conventional tests including CHROMAgar Candida in the identification of Candida species was 97.5%. The use of CHROMAgar Candida medium is an easy and accurate method for presumptive identification of the most commonly encountered Candida spp. PMID:24948942

  9. Stability of the elbow joint: relevant anatomy and clinical implications of in vitro biomechanical studies

    NARCIS (Netherlands)

    de Haan, J.; Schep, N. W. L.; Eygendaal, D.; Kleinrensink, G.-J.; Tuinebreijer, W. E.; den Hartog, D.


    The aim of this literature review is to describe the clinical anatomy of the elbow joint based on information from in vitro biomechanical studies. The clinical consequences of this literature review are described and recommendations are given for the treatment of elbow joint dislocation.The PubMed

  10. Description of Groenewaldozyma gen. nov. for placement of Candida auringiensis, Candida salmanticensis and Candida tartarivorans. (United States)

    Kurtzman, Cletus P


    DNA sequence analyses have demonstrated that species of the polyphyletic anamorphic ascomycete genus Candida may be members of described teleomorphic genera, members of the Candida tropicalis clade upon which the genus Candida is circumscribed, or members of isolated clades that represent undescribed genera. From phylogenetic analysis of gene sequences from nuclear large subunit rRNA, mitochondrial small subunit rRNA and cytochrome oxidase II, Candida auringiensis (NRRL Y-17674(T), CBS 6913(T)), Candida salmanticensis (NRRL Y-17090(T), CBS 5121(T)), and Candida tartarivorans (NRRL Y-27291(T), CBS 7955(T)) were shown to be members of an isolated clade and are proposed for reclassification in the genus Groenewaldozyma gen. nov. (MycoBank MB 815817). Neighbouring taxa include species of the Wickerhamiella clade and Candida blankii.

  11. Study of photoacoustic measurement of bone health based on clinically relevant models (United States)

    Feng, Ting; Kozloff, Ken; Cao, Meng; Cheng, Qian; Yuan, Jie; Wang, Xueding


    Photoacoustic (PA) technique involving both ultrasound and light has been explored for potential application in the assessment of bone health. The optical and ultrasound penetration in bone have been studied. The feasibility of conducting 3D PA imaging of bone, and performing quantitative evaluation of bone microstructures by using photoacoustic spectrum analysis (PASA) has also been investigated. The findings from the experiments demonstrate that PA measurement could offer information of bone mineral density and bone microstructure, both relevant to bone health.

  12. Produção de fatores de virulência in vitro por espécies patogênicas do gênero Candida Production of virulence factors in vitro by pathogenic species of the genus Candida

    Directory of Open Access Journals (Sweden)

    Kelly Cristina Ortolan Rörig


    Full Text Available Avaliou-se, in vitro, a capacidade de crescimento em 39ºC e 42ºC, a produção de enzimas hidrolíticas e a atividade hemolítica de 21 cepas clínicas e de referência de sete espécies de Candida spp, Candida dubliniensis e Candida krusei demonstraram menor potencial de virulência e Candida albicans maior.The growth capacity at 39ºC and 42ºC, production of hydrolytic enzymes and hemolytic activity of 21 clinical and reference strains of seven species of Candida spp were evaluated in vitro.Candida dubliniensis and Candida krusei demonstrated lower virulence potential and Candida albicans higher potential.

  13. Dependence and caring in clinical communication: the relevance of attachment and other theories. (United States)

    Salmon, Peter; Young, Bridget


    Clinical relationships are usually asymmetric, being defined by patients' dependence and practitioners' care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Attachment theory helps to understand patients' need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners' caring. Different theories that formulate practitioners' care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners' emotions, values and sense of role in understanding their clinical communication. Extending the theoretical grounding of clinical communication can accommodate patients' dependence and practitioners' caring without return to medical paternalism. A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be.

  14. Simplified sunflower (Helianthus annuus) seed agar for differentiation of Candida dubliniensis from Candida albicans. (United States)

    Khan, Z U; Ahmad, S; Mokaddas, E; Chandy, R


    This study evaluated sunflower (Helianthus annuus) seed agar (SSA) for differentiation of Candida dubliniensis from Candida albicans on the basis of colony characteristics and chlamydospore production. Simplified SSA without creatinine and KH(2)PO(4) was also used. On both media, C. dubliniensis isolates (n = 25) developed rough colonies and formed abundant chlamydospores after incubation for 24-48 h at 28 degrees C, while C. albicans isolates (n = 53) showed smooth colonies with no evidence of chlamydospore formation. Cryptococcus neoformans isolates (n = 10) formed brown colonies on both media. Simplified SSA offers a simple and inexpensive tool for presumptive differentiation of C. dubliniensis from C. albicans in clinical microbiology laboratories.

  15. Perspectives on creating clinically relevant blast models for mild traumatic brain injury and post traumatic stress disorder symptoms

    Directory of Open Access Journals (Sweden)

    Lisa eBrenner


    Full Text Available Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic, behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI and/or post traumatic stress disorder (PTSD. Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast TBI can be used to facilitate the development of clinically relevant blast models.

  16. Clinicopathologic assessment of Candida colonization of oral leukoplakia. (United States)

    Sarkar, Reena; Rathod, G P


    Leukoplakia is the most common premalignant lesion of the oral mucosa. We studied the colonization of Candida in oral leukoplakia using direct microscopy, culture and histopathology to determine if there is a statistical correlation between Candida invasion and the clinical appearance and presence of epithelial dysplasia in leukoplakia. Samples were collected from 40 patients with oral leukoplakia and 21 controls. The swabs collected were used to inoculate Sabouraud's dextrose agar slant and for direct microscopy with Gram's stain. Culture growths were subjected to germ tube and corn meal agar tests to differentiate between Candida albicans and non-albicans groups. Biopsies were also done in all patients for histopathological confirmation; Gomori's methanamine silver stain was used to identify fungal invasion of lesional epithelium. Nineteen cases of leukoplakia showed Candida on direct smears, compared to 3 controls. Eighteen cases and one control showed growth of Candida on culture. Non-homogenous leukoplakia showed a higher positivity rate on microscopy and culture than homogenous lesions. All these correlations were statistically significant. Forty percent of leukoplakia cases were simultaneously positive for Candida on direct microscopy, culture and histopathologic evaluation. No significant difference was found between non-dysplastic and distinctly dysplastic lesions with respect to Candida detection on microscopy or culture.

  17. Antifungal activity of extracts and isolated compounds from Buchenavia tomentosa on Candida albicans and non-albicans. (United States)

    Teodoro, Guilherme R; Brighenti, Fernanda L; Delbem, Alberto C Botazzo; Delbem, Ádina Cléia B; Khouri, Sonia; Gontijo, Aline Vidal L; Pascoal, Aislan Crf; Salvador, Marcos J; Koga-Ito, Cristiane Y


    This study aimed to evaluate the antifungal activity of Buchenavia tomentosa extract and bioactive compounds on six Candida species. The antimicrobial activity of extract was evaluated using standard strains and clinical isolates. Cytotoxicity was tested in order to evaluate cell damage caused by the extract. Extract was chemically characterized and the antifungal activity of its compounds was evaluated. Extract showed antifungal activity on Candida species. Candida non-albicans were more susceptible than Candida albicans. Low cytotoxicity for extract was observed. The isolated compounds presented antifungal activity at least against one Candida spp. and all compounds presented antifungal effect on Candida glabrata. Extracts from Buchenavia tomentosa showed promising antifungal activity on Candida species with low cytotoxicity. Gallic acid, corilagin and ellagic acid showed promising inhibitory activity on Candida glabrata.

  18. [The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014]. (United States)

    Giraldo, Newar A; Amariles, Pedro; Pino Marín, Daniel E; Faus, María José


    To update information about drug interactions in patients with HIV/AIDS. Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

  19. Rapid Discrimination between Candida glabrata, Candida nivariensis, and Candida bracarensis by Use of a Singleplex PCR ▿


    Enache-Angoulvant, A.; Guitard, J.; Grenouillet, F.; Martin, T; Durrens, P.; Fairhead, C.; Hennequin, C.


    We report here a PCR-based assay using a single primer pair targeting the RPL31 gene that allows discrimination between Candida glabrata, Candida bracarensis, and Candida nivariensis according to the size of the generated amplicon.

  20. Antifungal activity of linalool in cases of Candida spp. isolated from individuals with oral candidiasis

    Directory of Open Access Journals (Sweden)

    I. J. Dias


    Full Text Available Abstract This study analyzed the antifungal activity of phytoconstituents from linalool on Candida spp. strains, in vitro, isolated from patients with clinical diagnoses of oral candidiasis associated with the use of a dental prosthesis. Biological samples were collected from 12 patients using complete dentures or removable partial dentures and who presented mucous with diffuse erythematous or stippled features, indicating a clinical diagnosis of candidiasis. To identify fungal colonies of the genus Candida, samples were plated onto CHROMagar Candida®. The antifungal activity of linalool, a monoterpene unsaturated constituent of basil oil, was performed using the broth microdilution technique. Then, the minimum inhibitory concentration (MIC, the two subsequent stronger concentrations and the positive controls were subcultured on Sabouraud Dextrose Agar plates to determine the minimum fungicidal concentration (MFC. The experiments were performed in triplicate and nystatin was used as a positive control in all tests. Diagnoses of oral candidiasis were verified in eight patients (66.6% and the most prevalent fungal species was Candida albicans (37.5%, followed by Candida krusei (25.0%; and Candida tropicalis (4.2%. The best antifungal activity of linalool was observed on Candida tropicalis (MIC = 500 mg/mL, followed by Candida albicans (MIC = 1.000 mg/mL, and Candida krusei (MIC = 2.000 mg/mL.Under the study conditions and based on the results obtained, it can be concluded that the Candida strains tested were susceptible to linalool.

  1. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes


    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  2. Clinical relevance of cytogenetics to pediatric practice. Postnatal findings of Patau syndrome - Review of 5 cases. (United States)

    Plaiasu, Vasilica; Ochiana, Diana; Motei, Gabriela; Anca, Ioana; Georgescu, Adrian


    Patau syndrome (trisomy 13) is one of the most common chromosomal anomalies clinically characterized by the presence of numerous malformations with a limited survival rate for most cases. Babies are usually identified at birth and the diagnosis is confirmed with genetic testing. In this review we outline the clinical and cytogenetic aspects of trisomy 13 and associated phenotypes for 5 cases analyzed in the last 3 years, referred to our Clinical Genetics Department. For each child cytogenetic analysis was performed to determine the genetic variant; also, the patients were investigated for other associated malformations (cardiac, cerebral, renal, ocular anomalies). All 5 cases presented multiple malformations, including some but not all signs of the classical clinical triad suggestive of Patau syndrome. The cytogenetic investigation confirmed for each case the suspected diagnosis and also indicated the specific genetic variant, this being a valuable information for the genetic counselling of the families. The application of genetic analysis can increase diagnosis and prognosis accuracy and have an impact on clinical management.

  3. Putting the Pieces Together: Clinically Relevant Genetic and Genomic Resources for Hospitalists and Neonatologists. (United States)

    Miller, Rebecca; Khromykh, Alina; Babcock, Holly; Jenevein, Callie; Solomon, Benjamin D


    Genetic conditions are individually rare but are common in aggregate, and they often present in the neonatal and early pediatric periods. These conditions are often severe, can be difficult to diagnose and manage, and may heavily affect patients, families, health care systems, and society. Because of recent technological advances, the availability and uptake of genetic and genomic testing are increasing rapidly. However, there is a dearth of trained geneticists and genetic counselors to help guide and explain these conditions and relevant tests. To help hospitalists, neonatologists, and related practitioners navigate this complex and evolving field, we have compiled a list of free (mostly Web-based) resources relevant to the diagnosis and management of genetic conditions and related disorders. These resources, which we describe individually, can be useful for nongeneticist clinicians, and some also include material that can be used to explain concepts and conditions to patients or families. The resources presented are divided into the following categories (which overlap): general information, databases of genetic conditions, resources that can help generate differential diagnoses, databases of genetic testing laboratories (to help with logistics of ordering tests), information on newborn screening, and other resources. We also include a separate list of helpful textbooks and manuals. We conclude with 2 examples describing how some of these resources would be used by a pediatric hospitalist or neonatologist during the inpatient management of a child with a suspected genetic condition. Copyright © 2017 by the American Academy of Pediatrics.

  4. The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings (United States)

    de Boer, Marrit K.; Castelein, Stynke; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus


    A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce. PMID:25721311

  5. Protease and phospholipase activities of Candida spp. isolated from cutaneous candidiasis. (United States)

    Ramos, Lívia de Souza; Barbedo, Leonardo Silva; Braga-Silva, Lys Adriana; dos Santos, André Luis Souza; Pinto, Marcia Ribeiro; Sgarbi, Diana Bridon da Graça


    Cases of superficial and invasive mycoses caused by emerging species of Candida have been increasingly reported over the last thirty years. The production of hydrolytic enzymes plays a central role in the fungal infective process. In Candida infections the secretion of both proteases and phospholipases are well-known virulence attributes. To determine the protease and phospholipase production from 58 human clinical isolates of Candida obtained from individuals with cutaneous candidiasis seen in the Human and Veterinary Diagnostic Mycology Sector from Universidade Federal Fluminense (UFF), Brazil, from November 2008 to August 2009. Fungal identification was performed using biochemical tests. Proteolytic activity was detected on agar plates containing bovine serum albumin, and phospholipase production was determined on egg-yolk plates. The Candida species isolated were Candida parapsilosis (27.59%), Candida famata (18.96%), Candida albicans (15.52%), Candida haemulonii (12.06%), Candida ciferri (8.62%), Candida guilliermondii (6.90%), Candida tropicalis (5.17%) and Candida lipolytica (5.17%). All isolates of C. albicans produced both protease and phospholipase. As regards the isolates of non-C. albicans Candida species, 53.06% and 4.08% were able to produce protease and phospholipase, respectively. For example, the majority of isolates of C. parapsilosis (15/16) produced protease, while 40% of C. ciferri isolates (2/5) were phospholipase producers. This study shows, for the first time, that C. ciferri and C. haemulonii strains were able to produce protease. Collectively, our results showed that different species of Candida isolated from cutaneous lesions were able to produce proteases and/or phospholipases, which are multifunctional molecules directly involved in the infectious process of these fungi. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  6. Interspecies differences of candida species causing recurrent vulvovaginal candidiasis in response to fluconazole treatment

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    Siamak Naji


    Methods: The cross-sectional study was performed at Kowsar Gynecology Center, Motahhari educational hospital and Medical Mycology Center, Faculty of Medicine, Urmia, Iran, from October 2013 to July 2015. Those patients referred to the clinic with symptoms of vaginal discharge, itching or burning that swab samples from endo-exocervix and distal fornix discharge were taken. The vaginal discharge samples submitted to Medical Mycology Center, Urmia School of Medicine for the direct microscopic examination and cultures. Identification at the level of species was performed using CHROMagar Candida and Corn meal agar media. The molecular test polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP used for confirming culture results. For the susceptibility assay, disc diffusion method was performed with fluconazole and clotrimazole. Results: In these study 198 samples collected from patients with symptoms of vulvovaginal candidiasis, 77 vulvovaginal candidiasis cases were identified. Candida species are common in primary and recurrent cases in terms of frequency, Candida albicans (85.7%, Candida krusei (10.2% and Candida glabrata (4.1% were identified respectively. Total of 27 cases of recurrent vulvovaginal candidiasis, 10 cases were resistant to both clotrimazole and fluconazole (37% was observed that the most common species are resistant to treatment were Candida albicans by (82.1%, Candida krusei (14.3% and Candida glabrata (3.6% respectively. Drug resistance in Candida albicans, Candida krusei and Candida glabrata causing recurrent vulvovaginal candidiasis included 69.1%, 75% and 100% respectively. Conclusion: Our findings have shown frequency of resistant non-albicans Candida species to fluconazole and clotrimazole is increasing. There is a considerable difference between Candida albicans and non-albicans species, Candida glabrata for the resistance to fluconazole and clotrimazole.

  7. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

    Directory of Open Access Journals (Sweden)

    Susana ede Sola


    Full Text Available The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome(DS has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining

  8. A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials. (United States)

    de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; Del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara


    The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of

  9. Molecular Classification of Diffuse Large B-cell Lymphoma: What Is Clinically Relevant? (United States)

    Sujobert, Pierre; Salles, Gilles; Bachy, Emmanuel


    Major progress in the understanding of diffuse large B-cell lymphoma (DLBCL) biology has been made in the last decade. Many specific compounds have now entered early phase clinical trials. However, further efforts are needed to find an accurate, fast, reproducible, and affordable technique to translate DLBCL subtype determination by gene expression profiles into clinical application. This article discusses the advantages and drawbacks of the currently available techniques of DLBCL subtype determination as well as important prognostic implications related to the cell of origin. Furthermore, the article provides a schematic description of how molecularly defined DLBCL subtypes could guide tailored therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Candida/Candida biofilms. First description of dual-species Candida albicans/C. rugosa biofilm. (United States)

    Martins, Carlos Henrique Gomes; Pires, Regina Helena; Cunha, Aline Oliveira; Pereira, Cristiane Aparecida Martins; Singulani, Junya de Lacorte; Abrão, Fariza; Moraes, Thais de; Mendes-Giannini, Maria José Soares


    Denture liners have physical properties that favour plaque accumulation and colonization by Candida species, irritating oral tissues and causing denture stomatitis. To isolate and determine the incidence of oral Candida species in dental prostheses, oral swabs were collected from the dental prostheses of 66 patients. All the strains were screened for their ability to form biofilms; both monospecies and dual-species combinations were tested. Candida albicans (63 %) was the most frequently isolated microorganism; Candida tropicalis (14 %), Candida glabrata (13 %), Candida rugosa (5 %), Candida parapsilosis (3 %), and Candida krusei (2 %) were also detected. The XTT assay showed that C. albicans SC5314 possessed a biofilm-forming ability significantly higher (p biofilm was less than the total CFU of a monospecies C. albicans biofilm. In contrast to the profuse hyphae verified in monospecies C. albicans biofilms, micrographies showed that the C. albicans/non-albicans Candida biofilms consisted of sparse yeast forms and profuse budding yeast cells that generated a network. These results suggested that C. albicans and the tested Candida species could co-exist in biofilms displaying apparent antagonism. The study provide the first description of C. albicans/C. rugosa mixed biofilm. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  11. The Candida Pathogenic Species Complex (United States)

    Turner, Siobhán A.; Butler, Geraldine


    Candida species are the most common causes of fungal infection. Approximately 90% of infections are caused by five species: Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei. Three (C. albicans, C. tropicalis, and C. parapsilosis) belong to the CTG clade, in which the CTG codon is translated as serine and not leucine. C. albicans remains the most commonly isolated but is decreasing relative to the other species. The increasing incidence of C. glabrata is related to its reduced susceptibility to azole drugs. Genome analysis suggests that virulence in the CTG clade is associated with expansion of gene families, particularly of cell wall genes. Similar independent processes took place in the C. glabrata species group. Gene loss and expansion in an ancestor of C. glabrata may have resulted in preadaptations that enabled pathogenicity. PMID:25183855

  12. Candida Infection of the Bloodstream - Candidemia (United States)

    Candida Infection of the Bloodstream– Candidemia Fungal Disease Series #4 Candida is the single most important cause of fungal infections worldwide. In the U.S., Candida is the 4th most common cause of bloodstream ...

  13. [Interatrial block and its clinical relevance. Renaissance of an ECG change]. (United States)

    Tomcsányi, János


    Interatrial block involves conduction delay between the right and left atria during sinus rhythm. The review describes the classification, pathomechanism and clinical significance of this under-recognised ECG sign, nominated Bayés syndrome. The presented ECGs help to recognise the differentypes of interatrial blocks. Orv Hetil. 2018; 159(3): 91-95.

  14. Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine. (United States)

    Bray, Christopher; Bell, Lauren N; Liang, Hong; Haykal, Rasha; Kaiksow, Farah; Mazza, Joseph J; Yale, Steven H


    Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used laboratory markers of systemic inflammation. A thorough understanding of the similarities and differences between these two serological markers, including factors that affect measurements, is necessary for the proper utilization and interpretation of ESR and CRP. This review summarizes the current published literature (searched on MEDLINE through February 2016) surrounding the history and utilization of ESR and CRP, and examines factors that affect ESR and CRP measurements and discordance amongst these two inflammatory markers. As ESR and CRP lack sensitivity or specificity, these tests should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions. The clinical application of these tests in diagnosis is best applied to conditions in which there is high or low clinical probability of disease. Importantly, discrepancies between ESR and CRP measurements commonly have been reported in both inpatient and outpatient settings and this problem may be particularly prevalent in chronic inflammatory diseases. Numerous physiological factors, including noninfectious conditions and resolution of inflammation can contribute to abnormally high ESR/low CRP readings or vice versa. Although discordance may be encountered in certain settings, proper utilization of ESR and CRP measurements continues to play an important role in clinical management of many inflammatory and other conditions.

  15. The relevance of clinical and radiographic features of jaw lesions: A prospective study

    Directory of Open Access Journals (Sweden)

    Juliane Piragine ARAUJO

    Full Text Available Abstract The study was carried out in a Brazilian population and the aim was to describe the prevalence and the clinic-radiographical features of jaw lesions. In addition, a comparison between the main diagnosis hypothesis and final diagnosis was accessed. A prospective study which evaluated all patients with jaw lesions diagnosed in an Oral Diagnosis Center, between August 2013 and October 2014. A total of 450 patients were observed for the first time, and 130 had some type of jaw lesion. The mean age of the patients was 35.2 years ± 17.86. Among these, 71 were women (54.62% and 87 were Caucasian (66.92%. The mandible was affected more frequently (71.43% than the maxilla (28.57%. Swelling and pain were the most frequent clinical signs and symptoms and were observed in 60 (42.85% and 38 (27.14% cases, respectively. The panoramic x-ray was the main radiographic exam utilized (88.57%. Radiolucent lesions accounted for 89 cases (63.57% and the unilocular form was present in 114 cases (81.43%. A total of 93 cases had histopathological analyses and the periapical cyst was the most frequent lesion. In the other 47 lesions, the diagnosis was conducted by clinical and radiographic management. Bone lesions were frequent, being noted on first visit in approximately 30% of patients; in 1/3 of the cases, the diagnoses were completed with a combination of clinical and radiographic exams.

  16. Quantitative 3D high resolution transmission ultrasound tomography: creating clinically relevant images (Conference Presentation) (United States)

    Wiskin, James; Klock, John; Iuanow, Elaine; Borup, Dave T.; Terry, Robin; Malik, Bilal H.; Lenox, Mark


    There has been a great deal of research into ultrasound tomography for breast imaging over the past 35 years. Few successful attempts have been made to reconstruct high-resolution images using transmission ultrasound. To this end, advances have been made in 2D and 3D algorithms that utilize either time of arrival or full wave data to reconstruct images with high spatial and contrast resolution suitable for clinical interpretation. The highest resolution and quantitative accuracy result from inverse scattering applied to full wave data in 3D. However, this has been prohibitively computationally expensive, meaning that full inverse scattering ultrasound tomography has not been considered clinically viable. Here we show the results of applying a nonlinear inverse scattering algorithm to 3D data in a clinically useful time frame. This method yields Quantitative Transmission (QT) ultrasound images with high spatial and contrast resolution. We reconstruct sound speeds for various 2D and 3D phantoms and verify these values with independent measurements. The data are fully 3D as is the reconstruction algorithm, with no 2D approximations. We show that 2D reconstruction algorithms can introduce artifacts into the QT breast image which are avoided by using a full 3D algorithm and data. We show high resolution gross and microscopic anatomic correlations comparing cadaveric breast QT images with MRI to establish imaging capability and accuracy. Finally, we show reconstructions of data from volunteers, as well as an objective visual grading analysis to confirm clinical imaging capability and accuracy.

  17. Matrix metalloproteinases in gastric inflammation and cancer : clinical relevance and prognostic impact

    NARCIS (Netherlands)

    Kubben, Francois Jozef Gerard Marie


    The studies in this thesis describe the clinical impact of several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in H. pylori-induced gastritis and gastric cancer. In patients with H. pylori-induced gastritis, significantly increased mucosal MMP-9 levels were

  18. Risk factors for the development of clinical leprosy among contacts, and their relevance for targeted interventions

    NARCIS (Netherlands)

    Moet, F. J.; Meima, A.; Oskam, L.; Richardus, J. H.


    Existing knowledge on risk factors for the development of clinical leprosy among contacts of known leprosy patients is reviewed with the aim to identify factors associated with leprosy among contacts that have potential for developing effective targeted interventions in leprosy control. Different

  19. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial (United States)


    on the commercial use of the molecular diagnostics. What was the impact on society beyond science and technology ? Successful execution of this...clinical practice to predict aggressive disease. The accuracy of each biomarker for predicting short- and long-term progression will be characterized...multiple established and analytically validated quantitative molecular biomarkers to predict PCa progression in a multi- center active surveillance

  20. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance : A Review

    NARCIS (Netherlands)

    Kamal, Rama M; van Noorden, Martijn S; Franzek, Ernst; Dijkstra, Boukje A G; Loonen, Antonius; De Jong, Cornelius A J


    OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  1. The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review

    NARCIS (Netherlands)

    Kamal, R.M.; Noorden, M.S. van; Franzek, E.; Dijkstra, B.A.; Loonen, A.J.; Jong, C.A.J. de


    OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  2. The neurobiological mechanisms of gamma-hydroxybutyrate dependence and withdrawal and their clinical relevance: A review

    NARCIS (Netherlands)

    Kamal, R.M.; Noorden, M.S. van; Franzek, E.; Dijkstra, B.A.G.; Loonen, A.J.M.; Jong, C.A.J. de


    Objective: gamma-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the

  3. Salient features of the coronary collateral circulation and its clinical relevance. (United States)

    Stoller, Michael; Seiler, Christian


    The coronary collateral circulation provides an alternative source of blood supply to myocardium jeopardised by ischaemia. Collaterals enlarge with obstructive coronary artery disease to allow bulk flow, but blood flow deliverable by the native, pre-formed collateral extent can already be sizeable. Genetic determinants contribute significantly to the wide variability observed in both native collateral extent and its capacity to enlarge, and the severity of the coronary stenosis is the most significant environmental determinant for collateral enlargement. The protective effect of a well-developed coronary collateral circulation translates into relevant improvements in all-cause and cardiac mortality in the acute and chronic phases of coronary artery disease, as well as into a reduction of future adverse cardiovascular events.

  4. Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome (United States)

    Bialosky, Joel E.; Robinson, Michael E.


    Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm

  5. Evolution and Application of Inteins in Candida species: a Review

    Directory of Open Access Journals (Sweden)

    José Alex Lourenço Fernandes


    Full Text Available Inteins are invasive intervening sequences that perform an autocatalytic splicing from their host proteins. Among eukaryotes, these elements are present in many fungal species, including those considered opportunistic or primary pathogens, such as Candida spp. Here we reviewed and updated the list of Candida species containing inteins in the genes VMA, THRRS and GLT1 and pointed out the importance of these elements as molecular markers for molecular epidemiological researches and species-specific diagnosis, since the presence, as well as the size of these inteins, is polymorphic among the different species. Although absent in Candida albicans, these elements are present in different sizes, in some environmental Candida spp. and also in most of the non-albicans Candida spp. considered emergent opportunistic pathogens. Besides, the possible role of these inteins in yeast physiology was also discussed in the light of the recent findings on the importance of these elements as post-translational modulators of gene expression, reinforcing their relevance as alternative therapeutic targets for the treatment of non-albicans Candida infections, because, once the splicing of an intein is inhibited, its host protein, which is usually a housekeeping protein, becomes nonfunctional.

  6. Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species. (United States)

    Springer, Jan; Goldenberger, Daniel; Schmidt, Friderike; Weisser, Maja; Wehrle-Wieland, Elisabeth; Einsele, Hermann; Frei, Reno; Löffler, Jürgen


    PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n = 17). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n = 10). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

  7. Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis. (United States)

    Laban, Kamil G; Vergouwen, Mervyn D I; Dijkhuizen, Rick M; Sena, Emily S; Macleod, Malcolm R; Rinkel, Gabriel J E; van der Worp, H Bart


    In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

  8. NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection. (United States)

    Dikshit, N; Kale, S D; Khameneh, H J; Balamuralidhar, V; Tang, C Y; Kumar, P; Lim, T P; Tan, T T; Kwa, A L; Mortellaro, A; Sukumaran, B


    The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A. baumannii infection is unknown. Using a sublethal mouse pneumonia model, we demonstrate that an extensively drug-resistant clinical isolate (ICII) of A. baumannii exhibits reduced/delayed early pulmonary neutrophil recruitment, higher lung persistence, and, most importantly, elicits enhanced IL-1β/IL-18 production and lung damage through NLRP3 inflammasome, in comparison with A. baumannii-type strain. A. baumannii infection-induced IL-1β/IL-18 production is entirely dependent on NLRP3-ASC-caspase-1/caspase-11 pathway. Using Nlrp3 -/- mice infection models, we further show that while NLRP3 inflammasome pathway contributes to host defense against A. baumannii clinical isolate, it is dispensable for protection against A. baumannii-type strain. Our study reveals a novel differential role for NLRP3 inflammasome pathway in the immunity against clinically relevant A. baumannii infections, and highlights inflammasome pathway as a potential immunomodulatory target.

  9. Laboratory-Based Investigation of Denture Sonication Method in Patients with Candida-Associated Denture Stomatitis. (United States)

    Perić, Mirjana; Radunović, Milena; Pekmezović, Marina; Marinković, Jelena; Živković, Rade; Arsić Arsenijević, Valentina


    Denture stomatitis (DS) is a disease characterized by inflammation and erythema of the oral mucosa areas covered by the denture. Multifactorial etiological factors contribute to DS, but it seems that Candida plays the key role. The aim of the study was to evaluate the denture sonication method to: (i) increase the possibility of diagnosing patients with Candida-associated DS; (ii) detect and identify the mixed Candida spp., and (iii) determine the Candida colony forming units (CFU) and its possible relationship with DS severity, based on Newton's classification. The cross-sectional study conducted at the Clinic for Dental Prosthetics, Belgrade (Serbia) from June 2013 to December 2014 enrolled edentulous patients with dentures (n = 250). Patients without DS (n = 20) were the control group (CG). The patients' data were collected, and patients with DS (study group/SG) were selected and divided into SG Candida+ and SG Candida-. Based on severity of DS, the SG patients were classified in 3 groups (Newton's classification). Four sampling methods were applied to detect patients with Candida-associated DS: mucosa swab, denture swab, oral rinse, and denture sonication method. The sensitivity and specificity of denture sonication method were shown using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). In 97 (38.8%), out of 250 clinically examined patients, DS was diagnosed. In 82 (84.5%), out of 97 mycologically examined patients, Candida-associated DS was detected when denture sonication method was applied. Additionally, using the denture sonication method we observed: (i) the largest number of Candida positive patients compared to other sampling methods (p method is easy, accurate, and sensitive, and increases the possibility of diagnosing patients with Candida-associated DS. Additionally, yeast quantification, mixed Candida spp., and non-albicans Candida were detectable when cultivation on Candida CHROMagar was performed. It was not

  10. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. (United States)

    Della Porta, Matteo Giovanni; Malcovati, Luca; Boveri, Emanuela; Travaglino, Erica; Pietra, Daniela; Pascutto, Cristiana; Passamonti, Francesco; Invernizzi, Rosangela; Castello, Alessandro; Magrini, Umberto; Lazzarino, Mario; Cazzola, Mario


    We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value. Three hundred one consecutive patients were retrospectively evaluated for BM fibrosis and CD34 immunoreactivity. Marrow fibrosis was assessed following the European consensus guidelines. Moderate to severe BM fibrosis was detected in 17% of cases and was associated with multilineage dysplasia (P = .001), high transfusion requirement (P WHO categories with excess of blasts (P according to International Prognostic Scoring System and WHO classification-based Prognostic Scoring System categories, BM fibrosis involved a shift to a one-step more advanced risk group. BM fibrosis identifies a distinct subgroup of MDS with multilineage dysplasia, high transfusion requirement, and poor prognosis and represents an independent prognostic factor that may be useful in clinical decision making. Furthermore, the presence of CD34+ cell clusters is an independent risk factor for progression to acute leukemia.

  11. [Basic symptoms in schizophrenia, their clinical study and relevance in research]. (United States)

    Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes


    Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

  12. Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples

    DEFF Research Database (Denmark)

    Fackenthal, James D; Yoshimatsu, Toshio; Zhang, Bifeng


    BACKGROUND: BRCA1 and BRCA2 are the two principal tumour suppressor genes associated with inherited high risk of breast and ovarian cancer. Genetic testing of BRCA1/2 will often reveal one or more sequence variants of uncertain clinical significance, some of which may affect normal splicing...... patterns and thereby disrupt gene function. mRNA analyses are therefore among the tests used to interpret the clinical significance of some genetic variants. However, these could be confounded by the appearance of naturally occurring alternative transcripts unrelated to germline sequence variation...... or defects in gene function. To understand which novel splicing events are associated with splicing mutations and which are part of the normal BRCA2 splicing repertoire, a study was undertaken by members of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium...

  13. The epidemiology of Candida species associated with vulvovaginal candidiasis in an Iranian patient population. (United States)

    Mahmoudi Rad, M; Zafarghandi, S; Abbasabadi, B; Tavallaee, M


    Vulvovaginal candidiasis is a common infection among women worldwide. According to previous epidemiological studies, Candida albicans is the most common species of Candida. The prevalence of non-Candida species, however, is increasing. Identification of Candida species among the population will not only help health professionals to choose suitable antifungal treatments, but also prevent development of drug resistance. The aim of this study was to identify, using chromogenic agar medium, the Candida species associated with vulvovaginal candidiasis among a sample of the Iranian population. In a prospective cohort study during a two year period from March 2006 to March 2008, swab samples of vaginal discharge/secretion were taken from 200 patients admitted to the gynecology clinic of Mahdieh Hospital (Tehran, Iran) with a clinical presentation suggestive of vulvovaginal candidiasis. The isolates obtained were cultured on Sabouraud dextrose agar and chromogenic agar medium. Candida species were also identified by germ tube formation in serum, chlamydospore production on Corn Meal Agar and carbohydrate absorption using the API 20C-AUX kit. Participants were asked to complete a questionnaire investigating the risk factors associated with candidiasis. An assessment of the different species of recurrent and non-recurrent candidiasis was also made. Descriptive statistics, chi-square test, and t-test were used to analyze the data. A total of 191 isolates were obtained from 175 vaginal specimens. Candida albicans accounted for 67% of the strains including single and mixed infections. The other identified species were Candida glabrata (18.3%), Candida tropicalis (6.8%), Candida krusei (5.8%), Candida parapsilosis (1.6%), and Candida guilliermondii (0.5%) respectively. Mixed infection with two or more species of Candida was seen in 10.3% of patients. The most common mixed cause was the combination of Candida albicans and Candida glabrata. Participants who were sexually active

  14. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology. (United States)

    Ferner, Robin E; Aronson, Jeffrey K


    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  15. Approaches to biofilm-associated infections: the need for standardized and relevant biofilm methods for clinical applications. (United States)

    Malone, Matthew; Goeres, Darla M; Gosbell, Iain; Vickery, Karen; Jensen, Slade; Stoodley, Paul


    The concept of biofilms in human health and disease is now widely accepted as cause of chronic infection. Typically, biofilms show remarkable tolerance to many forms of treatments and the host immune response. This has led to vast increase in research to identify new (and sometimes old) anti-biofilm strategies that demonstrate effectiveness against these tolerant phenotypes. Areas covered: Unfortunately, a standardized methodological approach of biofilm models has not been adopted leading to a large disparity between testing conditions. This has made it almost impossible to compare data across multiple laboratories, leaving large gaps in the evidence. Furthermore, many biofilm models testing anti-biofilm strategies aimed at the medical arena have not considered the matter of relevance to an intended application. This may explain why some in vitro models based on methodological designs that do not consider relevance to an intended application fail when applied in vivo at the clinical level. Expert commentary: This review will explore the issues that need to be considered in developing performance standards for anti-biofilm therapeutics and provide a rationale for the need to standardize models/methods that are clinically relevant. We also provide some rational as to why no standards currently exist.

  16. Markers of Oxidant Stress that are Clinically Relevant in Aging and Age-related Disease


    Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej R.; Evans, Michele K.


    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implicat...



    Hussein, Yaser R.; Sood, Anil K.; Bandyopadhyay, Sudeshna; Albashiti, Bassam; Semaan, Assaad; Nahleh, Zeina; Roh, Juwon; Han, Hee Dong; Lopez-Berestein, Gabriel; Ali-Fehmi, Rouba


    The polycomb group protein, enhancer of zeste homolog 2 (EZH2), is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the clinical and biological significance of EZH2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with EZH2, cytokeratin 5/6, epidermal growth factor receptor 1(EGFR) and p53. The expression of these markers was correlated with ...

  18. Planning clinically relevant biomarker validation studies using the "number needed to treat" concept. (United States)

    Day, Roger S


    Despite an explosion of translational research to exploit biomarkers in diagnosis, prediction and prognosis, the impact of biomarkers on clinical practice has been limited. The elusiveness of clinical utility may partly originate when validation studies are planned, from a failure to articulate precisely how the biomarker, if successful, will improve clinical decision-making for patients. Clarifying what performance would suffice if the test is to improve medical care makes it possible to design meaningful validation studies. But methods for tackling this part of validation study design are undeveloped, because it demands uncomfortable judgments about the relative values of good and bad outcomes resulting from a medical decision. An unconventional use of "number needed to treat" (NNT) can structure communication for the trial design team, to elicit purely value-based outcome tradeoffs, conveyed as the endpoints of an NNT "discomfort range". The study biostatistician can convert the endpoints into desired predictive values, providing criteria for designing a prospective validation study. Next, a novel "contra-Bayes" theorem converts those predictive values into target sensitivity and specificity criteria, to guide design of a retrospective validation study. Several examples demonstrate the approach. In practice, NNT-guided dialogues have contributed to validation study planning by tying it closely to specific patient-oriented translational goals. The ultimate payoff comes when the report of the completed study includes motivation in the form of a biomarker test framework directly reflecting the clinical decision challenge to be solved. Then readers will understand better what the biomarker test has to offer patients.

  19. Attentional bias modification based on visual probe task: methodological issues, results and clinical relevance

    Directory of Open Access Journals (Sweden)

    Fernanda Machado Lopes


    Full Text Available Introduction: Attentional bias, the tendency that a person has to drive or maintain attention to a specific class of stimuli, may play an important role in the etiology and persistence of mental disorders. Attentional bias modification has been studied as a form of additional treatment related to automatic processing. Objectives: This systematic literature review compared and discussed methods, evidence of success and potential clinical applications of studies about attentional bias modification (ABM using a visual probe task. Methods: The Web of Knowledge, PubMed and PsycInfo were searched using the keywords attentional bias modification, attentional bias manipulation and attentional bias training. We selected empirical studies about ABM training using a visual probe task written in English and published between 2002 and 2014. Results: Fifty-seven studies met inclusion criteria. Most (78% succeeded in training attention in the predicted direction, and in 71% results were generalized to other measures correlated with the symptoms. Conclusions: ABM has potential clinical utility, but to standardize methods and maximize applicability, future studies should include clinical samples and be based on findings of studies about its effectiveness.

  20. Direct oral anticoagulants and antiplatelet agents. Clinical relevance and options for laboratory testing. (United States)

    Sibbing, D; Spannagl, M


    Oral anticoagulants and platelet receptor blockers are widely used in clinical practice with the aim of reducing the risk of thrombotic complications in patients with cardiovascular diseases. Their regular intake and adequate antithrombotic action is vital and this is way numerous assays have been developed for laboratory testing and monitoring of these agents. Available assays can be stratified into pharmacokinetic and pharmacodynamic assays. Such assays are increasingly used in clinical routine and their daily use is triggered by the advent of the novel direct oral anticoagulants (DOACs) as an alternative for vitamin K antagonist (VKA) treatment, which are dabigatran, rivaroxaban and apixaban, and by the advent of prasugrel or ticagrelor as an alternative for clopidogrel with regard to platelet P2Y12 receptor inhibition. In this review the most important and most commonly used laboratory assays are summarized as well as their clinical implications with the focus on DOACs as an alternative for VKAs and the different P2Y12 receptor blockers for antiplatelet treatment.