Publications by authors named "Suleyman Yildirim"

30 Publications

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The effect of driving pressures in COVID-19 ARDS: Lower may still be better as in classic ARDS.

Respir Investig 2021 Sep 6;59(5):628-634. Epub 2021 Jul 6.

University of Health Sciences, Dr. Suat Seren Chest Disease and Chest Surgery Training and Research Hospital, Intensive Care Unit, İzmir, Turkey. Electronic address:

Background: The respiratory dynamics of coronavirus disease 2019 (COVID-19) patients under invasive ventilation are still not well known. In this prospective cohort, we aimed to assess the characteristics of the respiratory system in COVID-19 patients under invasive mechanical ventilation and evaluate their relationship with mortality.

Methods: Fifty-eight COVID-19 patients who underwent invasive mechanical ventilation between March 11, 2020 and September 1, 2020 were enrolled for the present study. Demographics and laboratory values at baseline were recorded. Respiratory variables such as tidal volume, plateau pressure, positive end expiratory pressure, static compliance, and driving pressure were recorded daily under passive conditions. Further, the median values were analyzed.

Results: Median age of the patients was 64 years (58-72). Mortality was 60% on day 28. Plateau pressure, driving pressure, and static compliance significantly differ between the survivors and non-survivors. When patients were categorized into two groups based on the median driving pressure (Pdrive) of ≤15 cmHO or >15 cmHO during their invasive mechanical ventilation period, there was significantly better survival on day 28 in patients having a Pdrive ≤ 15 cmHO [28 days (95% CI = 19-28) vs 16 days (95% CI = 6-25), (log-rank p = 0.026).

Conclusion: COVID-19 related acute respiratory distress syndrome (ARDS) seemed to have similar characteristics as other forms of ARDS. Lung protective ventilation with low plateau and driving pressures might be related to lower mortality.
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http://dx.doi.org/10.1016/j.resinv.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258546PMC
September 2021

Cost of Chronic Critically Ill Patients to the Healthcare System: A Single-center Experience from a Developing Country.

Indian J Crit Care Med 2021 May;25(5):519-523

Department of Intensive Care Unit, University of Health Sciences, Turkey, Dr Suat Seren Chest Diseases and Chest Surgery Training and Research Hospital, İzmir, Turkey.

Background: An increasing number of patients become chronic critically ill (CCI) and dependent on long-term therapies in the intensive care unit (ICU). Mortality and healthcare costs increase in these patients. In order to deal with this problem, the magnitude and risk factors for CCI must first be determined. Therefore, we aimed at evaluating the incidence cost and risk factors for CCI in our ICU.

Materials And Methods: This retrospective cohort study was compiled by recruiting patients admitted to our ICU between January 1, 2017, and December 31, 2018. Patients with an ICU stay of more than 21 days were defined as CCI. Patients who did not survive in the first 21 days were excluded from the study because it could be not known whether these patients would progress to CCI. During the study period, 1,166 patients were followed up, and 475 (40%) of them were excluded and 691 patients were included in the final analyses.

Results: During the study period, 691 patients were included in the study and 152 of them (22%) were CCI. Age, acute physiology and chronic health evaluation (APACHE)-2 score, length of stay, and daily costs were higher in patients with CCI. The cost for a patient with CCI is sixfold that of a patient without CCI. ICU mortality was 47% in patients without CCI and 54% in the CCI patients ( < 0.001).

Conclusion: CCI affects an increasing number of patients and leads to increased mortality rates and cost. Prolonged duration in ICU may cause complications such as secondary infections, sepsis episodes, and acute renal injury. The treatment of these complications may lead to increased mortality and cost.

How To Cite This Article: Yildirim S, Durmaz Y, Şan Y, Taşkiran İ, Cinleti BA, Kirakli C. Cost of Chronic Critically Ill Patients to the Healthcare System: A Single-center Experience from a Developing Country. Indian J Crit Care Med 2021;25(5):519-523.
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http://dx.doi.org/10.5005/jp-journals-10071-23804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196383PMC
May 2021

Role of serum organic solute transporter alpha/beta and sodium taurocholate cotransporting polypeptide in intrahepatic cholestasis of pregnancy.

Ginekol Pol 2021 Apr 12. Epub 2021 Apr 12.

Department of Gastroenterology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey.

Objectives: This study aimed to assess the role of OST-α, OST-β and NTCP in patients with ICP, with a view to determine patients with severe prognosis and to minimize adverse fetal outcomes.

Material And Methods: Sixty-nine pregnant women diagnosed with ICP and 50 healthy women were included the study. Serum OST-α, OST-β and NTCP were measured using ELISA kits.

Results: The median OST-α levels were 176.3 pg/mL in women with ICP and 201 pg/mL in healthy subjects (p = 0.205). The median OST-β levels were found to be 51.17 pg/mL in patients with ICP and 40.9 pg/mL in controls (p = 0.033). Median NTCP levels were 519.7 ng/mL in the ICP group and 483.3 ng/mL in healthy women (p = 0.051).

Conclusions: This is the first study to evaluate serum levels of OST-α, OST-β and NTCP in patients with ICP. It is likely that OST-α, OST-β and NTCP contribute to the etiopathogenesis of ICP. Serum OST-α and OST-β levels can be used as diagnostic and monitoring markers of ICP, and the inhibition of these molecules could provide therapeutic benefit in ICP by reducing the circulation of enterohepatic bile acids.
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http://dx.doi.org/10.5603/GP.a2021.0063DOI Listing
April 2021

Microbiome and Longevity: High Abundance of Longevity-Linked Muribaculaceae in the Gut of the Long-Living Rodent .

OMICS 2020 10 9;24(10):592-601. Epub 2020 Sep 9.

Regenerative and Restorative Medicine Research Center, REMER, Istanbul Medipol University, Istanbul, Turkey.

With a world population living longer as well as marked disparities in life expectancy, understanding the determinants of longevity is one of the priority research agendas in 21st century life sciences. To this end, the blind mole-rat (), a subterranean mammalian, has emerged as an exceptional model organism due to its astonishing features such as remarkable longevity, hypoxia and hypercapnia tolerance, and cancer resistance. The microbiome has been found to be a vital parameter for cellular physiology and it is safe to assume that it has an impact on life expectancy. Although the unique characteristics of make it an ideal experimental model for longevity research, there is limited knowledge of the bacterial composition of microbiome, which limits its in-depth utilization. In this study, using 16S rRNA amplicon sequencing, we report the gut and skin bacterial structure of for the first time. The diversity between fecal and skin samples was manifested in the distant clustering, as revealed by beta diversity analysis. Importantly, the longevity-linked Muribaculaceae bacterial family was found to be the dominating bacterial taxa in fecal samples. These new findings contribute toward further development of as a model for longevity research and potential linkages between microbiome composition and longevity.
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http://dx.doi.org/10.1089/omi.2020.0116DOI Listing
October 2020

2019 Expert opinion on biological treatment use in inflammatory bowel disease management.

Turk J Gastroenterol 2019 11;30(Suppl 4):S913-S946

Department of Gastroenterology, İstanbul University-Cerrahpaşa Cerrahpaşa School of Medicine, İstanbul, Turkey.

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http://dx.doi.org/10.5152/tjg.2019.061119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372973PMC
November 2019

How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.

Ann Hematol 2020 Jun 5;99(6):1193-1203. Epub 2020 Mar 5.

Department of Internal Medicine, Division of Gastroenterology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.
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http://dx.doi.org/10.1007/s00277-020-03951-5DOI Listing
June 2020

Oxidant and antioxidant parameters in people who fast during Ramadan, and those who do not.

Afr Health Sci 2019 Sep;19(3):2713-2717

Harran University Faculty of Medicine, Department of Biochemistry, Şanlıurfa, Turkey.

Background: The main aim of this study was to compare, by a new automated colorimetric method, oxidant and anti-oxidant status of those who fast during Ramadan and those who do not. For this purpose, total oxidant status (TOS), total anti-oxidant capacity (TAC) levels and oxidative stress index (OSI) were analysed. By doing this, we hope to examine whether fasting has any beneficial effect on human health.

Materials And Methods: Fifty seven people were included in this study. Of these, 30 people had been fasting during the month of Ramadan for at least ten years, but 27 had never fasted in their life. On the 15 day of Ramadan, blood samples were obtained from both groups after 12 hours of fasting.

Results: The TAC levels of the fasting group (1.29±0,19) was quite higher than the non-fasting group (1,09±0,16) [EIC2][ICD3] [ICD4](p< 0.001). Similarly, in the fasting group TOS level and the OSI (respectively 12,77±2,23 and 1,01±0,25) was quite lower [EIC5][ICD6][ICD7] than in the non-fasting group (respectively 14,15±2,04 and 1,33±0,30), (p<=0.019 and p<0.001, respectively).These findings show that the TOS level of non-fasting group was high. This oxidative stress might cause various illnesses. Therefore, fasting could play a significant part in health-protection by increasing total anti-oxidant capacity.
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http://dx.doi.org/10.4314/ahs.v19i3.46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040294PMC
September 2019

Urinary microbiome in uncomplicated and interstitial cystitis: is there any similarity?

World J Urol 2020 Nov 31;38(11):2721-2731. Epub 2020 Jan 31.

Department of Urology, Medipol University Research Hospital, Istanbul, Turkey.

Purpose: Acute/uncomplicated cystitis is the most common bacterial infection causing inflammation in the bladder tissues and predominantly diagnosed in women. Interstitial cystitis may too, cause inflammation in the bladder but its etiology has been elusive. Even though the site and symptoms of both diseases are largely shared, state of the urinary microbiome in these disorders have not been comparatively evaluated before. The purpose of this review is to assess and qualitatively compare structure and composition of the urinary microbiome in acute/uncomplicated cystitis and interstitial cystitis.

Methods And Results: The available literature in MEDLINE are extensively searched using keywords and screened. Pertinent evidence is carefully assessed and synthesized. We included the original studies with a cohort of medically stable, non-pregnant women with otherwise functionally normal urinary tract and excluded the original articles if the infection in a patient's cohort is accompanied by urinary syndromes such as incontinence and overactive bladder syndrome. A total of six original papers reporting on the urinary microbiome in acute cystitis and nine papers on the interstitial cystitis met the selection criteria.

Conclusion: The evidence we have gleaned from the literature on the urinary microbiome associated with the acute and interstitial cystitis does not point to convergence of microbiome similarities between the two diseases. More studies with direct sampling of the bladder tissues besides sampling bladder surfaces are warranted for accurate comparison of microbiome similarity between the two conditions. The future research on interstitial cystitis microbiome should include stratified cohorts with prospective design.
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http://dx.doi.org/10.1007/s00345-020-03099-xDOI Listing
November 2020

Longitudinal 16S rRNA data derived from limb regenerative tissue samples of axolotl Ambystoma mexicanum.

Sci Data 2019 May 23;6(1):70. Epub 2019 May 23.

Department of Microbiology, International School of Medicine, İstanbul Medipol University, Istanbul, Turkey.

The Mexican axolotl (Ambystoma mexicanum) is a critically endangered species and a fruitful amphibian model for regenerative biology. Despite growing body of research on the cellular and molecular biology of axolotl limb regeneration, microbiological aspects of this process remain poorly understood. Here, we describe bacterial 16S rRNA amplicon dataset derived from axolotl limb tissue samples in the course of limb regeneration. The raw data was obtained by sequencing V3-V4 region of 16S rRNA gene and comprised 14,569,756 paired-end raw reads generated from 21 samples. Initial data analysis using DADA2 pipeline resulted in amplicon sequence variant (ASV) table containing a total of ca. 5.9 million chimera-removed, high-quality reads and a median of 296,971 reads per sample. The data constitute a useful resource for the research on the microbiological aspects of axolotl limb regeneration and will also broadly facilitate comparative studies in the developmental and conservation biology of this critically endangered species.
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http://dx.doi.org/10.1038/s41597-019-0077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533342PMC
May 2019

Transformation of Acinetobacter baumannii: Electroporation.

Methods Mol Biol 2019 ;1946:69-74

Department of Medical Microbiology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Although the pan and the core genome of Acinetobacter baumannii and its essential genes are relatively well characterized, functional characterization of these genes has not paralleled the genome-level studies. However, recently developed genetic tools and optimized protocols are poised to accelerate genetic manipulation of A. baumannii. Transferring exogenous DNA into the cytosol of bacteria cells is a critical step in genetic characterizations. Conjugation is restricted to the transfer of DNA from one bacterial cell to another, and only a portion of A. baumannii clinical isolates are naturally competent. Electroporation, which is thought to transiently create aqueous pores in the membrane, is a preferred method in transferring exogenous DNA as it does not have such limitations. Several factors contribute to efficiency of electroporation and often need to be empirically optimized to maximize efficiency of this procedure. Here we provide an optimized electroporation protocol and guidance for electroporation of clinical MDR isolates of A. baumannii.
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http://dx.doi.org/10.1007/978-1-4939-9118-1_7DOI Listing
July 2019

Experimentally induced metamorphosis in highly regenerative axolotl (ambystoma mexicanum) under constant diet restructures microbiota.

Sci Rep 2018 Jul 20;8(1):10974. Epub 2018 Jul 20.

Department of Microbiology, International School of Medicine, İstanbul Medipol University, Istanbul, Turkey.

Axolotl (Ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. Despite life-long neoteny in nature and in captive-bred colonies, metamorphosis of these animals can be experimentally induced by administering Thyroid hormones (THs). However, microbiological consequences of this experimental procedure, such as host microbiota response, remain largely unknown. Here, we systematically compared host bacterial microbiota associated with skin, stomach, gut tissues and fecal samples, between neotenic and metamorphic axolotls based on 16S rRNA gene sequences. Our results show that distinct bacterial communities inhabit individual organs of axolotl and undergo substantial restructuring through metamorphosis. Skin microbiota among others, shifted sharply, as highlighted by a major transition from Firmicutes-enriched to Proteobacteria-enriched relative abundance and precipitously decreased diversity. Fecal microbiota of neotenic and metamorphic axolotl shared relatively higher similarity, suggesting that diet continues to shape microbiota despite fundamental transformations in the host digestive organs. We also reproduced the previous finding on reduction in regenerative capacity in limbs of axolotl following metamorphosis, highlighting the need to investigate whether shifts in microbiota is causally linked to regenerative capacity of axolotl. The initial results on axolotl microbiota provide novel insights into microbiological aspects of axolotl metamorphosis and will establish a baseline for future in-depth studies.
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http://dx.doi.org/10.1038/s41598-018-29373-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054665PMC
July 2018

An Evaluation of the Information Sources of Cancer Patients' Relatives. A Prospective Survey.

J Cancer Educ 2019 Oct;34(5):913-919

School of Medicine, Department of Medical Oncology, Dokuz Eylul University, Inciralti, Izmir, Turkey.

Patients followed up with a cancer diagnosis must be well-informed about cancer to be able to cope with it. Besides, informing the relatives of the cancer patients who are also experiencing the same process about the diagnosis and follow-up period of cancer is highly important. In the current study, it was aimed to evaluate the information sources about cancer which are referred to by relatives of cancer patients. Three hundred ninety-one cancer patient relatives were included in medical oncology clinic between May 1 and June 30, 2015. A questionnaire was applied to the participants, comprising 12 questions to elicit demographic information and 11 questions about the information sources to which they referred. The study included 183 female and 208 male participants with a mean age of 47.9 ± 13.6 years. While the oncologists were the primary information sources referred to by 87%, the Internet was the second most preferred information source by 72%. The websites most frequently referred were the official websites (70%), the websites of oncology associations (53%), and social networks and forums (32%). The primary factors affecting the Internet preference were age, education level, income level, and place of residence. The Internet was the second most referred information source about cancer by family caregivers following oncologists. Therefore, it is of crucial importance that physicians inform patients and their relatives comprehensively as well as guiding them to correct and reliable information sources.
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http://dx.doi.org/10.1007/s13187-018-1395-8DOI Listing
October 2019

Serum α-Hydroxybutyrate: A Candidate Marker of Insulin Resistance Is Associated with Deterioration in Anthropometric Measurements in Individuals with Low Diabetes Risk.

J Appl Lab Med 2017 Mar;1(5):562-567

Department of Endocrinology and Metabolism, Yeditepe University Medical Faculty, Istanbul, Turkey.

Background: α-Hydroxybutyrate (α-HB) is a marker of insulin resistance (IR) and lipid oxidation, both of which precede the development of diabetes and cardiovascular disorders. We aimed to analyze the relation of α-HB levels with anthropometric measurements in individuals without metabolic risk factors.

Methods: A total of 82 nonobese individuals [body mass index (BMI) <30 kg/m2] without an accompanying chronic disorder were enrolled into the study. The entire cohort of participants underwent physical examination. Biochemical and hormonal parameters were analyzed. The BMI was calculated as weight/height2 (kg/m2). An ELISA method was used to analyze serum α-HB level. The relation of variables was analyzed by correlation analysis.

Results: The mean age, BMI, body fat ratio, and waist/hip ratio of participants were 36 (9) years, 24.9 (2.2), 39.2 (3.9), and 0.82 (0.06), respectively. The mean fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) levels, total cholesterol, triglyceride, HDL, and LDL levels were 90.7 (5.1) mg/dL, 9.8 (1.5) IU/mL, 2.2 (0.3), 193.2 (32.6) mg/dL, 119.3 (60.3) mg/dL, 54.6 (12.2) mg/dL, and 114.2 (30.4) mg/dL, respectively. Serum α-HB level was significantly correlated with age, BMI, body fat ratio, waist circumference, waist/hip ratio, fasting glucose, insulin, HOMA-IR, HDL, total cholesterol, and triglyceride.

Conclusions: Serum α-HB, a strong marker of insulin resistance, is well correlated with deterioration of anthropometric parameters such as an increase in BMI and body fat distribution in patients with low diabetes risk.
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http://dx.doi.org/10.1373/jalm.2016.021444DOI Listing
March 2017

Association of Enteric Protist Blastocystis spp. and Gut Microbiota with Hepatic Encephalopathy.

J Gastrointestin Liver Dis 2016 Dec;25(4):489-497

Medipol University International School of Medicine, Department of Medical Microbiology, İstanbul, Turkey.

Background And Aims: Hepatic encephalopathy (HE) is a serious neuropsychiatric sequela emerging in the advanced stages of cirrhosis. The gut microbiota plays an important role in the development of HE. The aim of the study was to analyze the dynamic interplay between microbiota and Blastocystis in cirrhotic patients with or without encephalopathy.

Methods: The study was designed as cross-sectional study. A total of 37 patients from the Ankara city, admitted to the University Hospital within a 6-month period prior to enrolment into the study were included in the study. After the regular health checks, clinical histories, clinical examinations, and Psychometric HE Score (PHES) points, patients' MELD and CTP scores were recorded. The fecal microbiota configurations were characterized by targeting hypervariable regions V3 and V4 of the 16S rRNA gene using Illumina MiSeq System.

Results: Blastocystis spp. were detected in 21.6% (n = 8) of all cirrhotic patients. When those were analyzed by subgroups, four of them were subtype 2, three were subtype 3 and one was subtype 1. Blastocystis spp. were not found in any of the patients with HE; however, they were detected in 38.1% of the patients without HE. Also the increase in the bacterial diversity was observed along with the absence of Blastocystis. It was suggested that there was an inverse relationship between Blastocystis spp. and advanced stages of HE and the structure and composition of gut microbiota.

Conclusion: The absence of Blastocystis spp. is associated with the HE severity and dysbiosis in the gut microbiota.
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http://dx.doi.org/10.15403/jgld.2014.1121.254.yizDOI Listing
December 2016

Evaluation of Parameters for High Efficiency Transformation of Acinetobacter baumannii.

Sci Rep 2016 Feb 25;6:22110. Epub 2016 Feb 25.

Department of Wound Infections, Bacterial Diseases Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

Acinetobacter baumannii is an emerging, nosocomial pathogen that is poorly characterized due to a paucity of genetic tools and methods. While whole genome sequence data from several epidemic and environmental strains have recently become available, the functional characterization of genes is significantly lagging. Efficient transformation is one of the first steps to develop molecular tools that can be used to address these shortcomings. Here we report parameters allowing high efficiency transformation of A. baumannii. Using a multi-factorial experimental design we found that growth phase, voltage, and resistance all significantly contribute to transformation efficiency. The highest efficiency (4.3 × 10(8) Transformants/μg DNA) was obtained at the stationary growth phase of the bacterium (OD 6.0) using 25 ng of plasmid DNA under 100 Ohms resistance and 1.7 kV/cm voltage. The optimized electroporation parameters reported here provide a useful tool for genetic manipulation of A. baumannii.
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http://dx.doi.org/10.1038/srep22110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766488PMC
February 2016

Genetic Manipulation of Acinetobacter baumannii.

Curr Protoc Microbiol 2014 Nov 3;35:6G.2.1-11. Epub 2014 Nov 3.

Walter Reed Army Institute of Research, Department of Wound Infections, Silver Spring, Maryland.

Acinetobacter baumannii is a Gram-negative nosocomial pathogen of clinical importance. A lack of genetic tools has hindered the research of this organism in the past; however, recently, various methods have been designed, modified, and optimized to facilitate the genetic manipulation of A. baumannii. This unit describes some of the recent genetic advances and new recombinant tools developed for this pathogen, including standard transformation and conjugation techniques specifically developed for the bacteria. As the need to understand the basic biology of A. baumannii increases with the prospect of developing new therapeutics, the use of the basic genetic methods herein can provide the critical first step to identify genes required for infection.
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http://dx.doi.org/10.1002/9780471729259.mc06g02s35DOI Listing
November 2014

Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance.

ISME J 2014 Dec 18;8(12):2431-44. Epub 2014 Jul 18.

1] The Institute for Genomic Biology, University of Illinois, Urbana, IL, USA [2] Department of Anthropology, University of Illinois, Urbana, IL, USA.

Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host-microbe variation and coevolution, microbial biogeography, and disease risk, and have important implications for the use of animal models in studies of human sexual and reproductive diseases.
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http://dx.doi.org/10.1038/ismej.2014.90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260710PMC
December 2014

Validation of a novel murine wound model of Acinetobacter baumannii infection.

Antimicrob Agents Chemother 2014 16;58(3):1332-42. Epub 2013 Dec 16.

Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifaceted in vivo assessment prior to testing in larger animals.
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http://dx.doi.org/10.1128/AAC.01944-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957858PMC
October 2014

The primate vaginal microbiome: comparative context and implications for human health and disease.

Am J Phys Anthropol 2013 Dec 28;152 Suppl 57:119-34. Epub 2013 Oct 28.

Department of Anthropology, University of Illinois, Urbana, IL; Institute for Genomic Biology, University of Illinois, Urbana, IL.

The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.
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http://dx.doi.org/10.1002/ajpa.22395DOI Listing
December 2013

Pilus gene pool variation and the virulence of Corynebacterium diphtheriae clinical isolates during infection of a nematode.

J Bacteriol 2013 Aug 14;195(16):3774-83. Epub 2013 Jun 14.

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas, USA.

Toxigenic Corynebacterium diphtheriae strains cause diphtheria in humans. The toxigenic C. diphtheriae isolate NCTC13129 produces three distinct heterotrimeric pili that contain SpaA, SpaD, and SpaH, making up the shaft structure. The SpaA pili are known to mediate bacterial adherence to pharyngeal epithelial cells. However, to date little is known about the expression of different pili in various clinical isolates and their importance in bacterial pathogenesis. Here, we characterized a large collection of C. diphtheriae clinical isolates for their pilin gene pool by PCR and for the expression of the respective pilins by immunoblotting with antibodies against Spa pilins. Consistent with the role of a virulence factor, the SpaA-type pili were found to be prevalent among the isolates, and most significantly, corynebacterial adherence to pharyngeal epithelial cells was strictly correlated with isolates that were positive for the SpaA pili. By comparison, the isolates were heterogeneous for the presence of SpaD- and SpaH-type pili. Importantly, using Caenorhabditis elegans as a model host for infection, we show here that strain NCTC13129 rapidly killed the nematodes, the phenotype similar to isolates that were positive for toxin and all pilus types. In contrast, isogenic mutants of NCTC13129 lacking SpaA-type pili or devoid of toxin and SpaA pili exhibited delayed killing of nematodes with similar kinetics. Consistently, nontoxigenic or toxigenic isolates that lack one, two, or all three pilus types were also attenuated in virulence. This work signifies the important role of pili in corynebacterial pathogenesis and provides a simple host model to identify additional virulence factors.
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http://dx.doi.org/10.1128/JB.00500-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754579PMC
August 2013

Evaluation of the serum cystatin C values in prediction of indications for hemodialysis in patients with chronic renal failure.

Int Urol Nephrol 2014 Jan 8;46(1):57-62. Epub 2013 Jun 8.

Clinic of Internal Medicine/Nephrology, Bagcilar Training and Research Hospital, 34200, Bagcılar, Istanbul, Turkey,

Background: Indications of dialysis treatment for patients with end-stage renal disease depend on various clinical and laboratory parameters. In this study, we aimed to determine whether standardized serum cystatin C (SCC) equation may be an applicability of marker for dialysis initiation and its relationship to other clearance values among patients with advanced chronic kidney disease.

Materials And Methods: A total of 84 patients (45 males, 39 females) aged 19-89 were evaluated in this study. Hemodialysis was indicated according to clinical and laboratory findings, and estimated glomerular filtration rate (eGFR) was according to four different formulas [MDRD, EpiCKD, Cockcroft Gault formula (CGF) and SCC equation].

Results: eGFR values of patients in the study were 7.23 ± 3.26, 7.86 ± 3.78, 15.09 ± 10.88 and 11.31 ± 4.54 according to MDRD, EpiCKD, SCC equation and CGF, respectively. There was a positive correlation between MDRD, EpiCKD and CGF, and between EpiCKD and CGF (p < 0.01). Also, statistically significant correlation was found between SCC equation and CGF (p < 0.05).

Conclusion: SCC equation was not seemed to be an appropriate marker for starting dialysis in patients with advanced CKD.
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http://dx.doi.org/10.1007/s11255-013-0481-4DOI Listing
January 2014

Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes.

ISME J 2013 Jul 14;7(7):1344-53. Epub 2013 Mar 14.

Program in Ecology, Evolution and Conservation Biology, University of Illinois, Urbana, IL, USA.

The gastrointestinal (GI) microbiome contributes significantly to host nutrition and health. However, relationships involving GI microbes, their hosts and host macrohabitats remain to be established. Here, we define clear patterns of variation in the GI microbiomes of six groups of Mexican black howler monkeys (Alouatta pigra) occupying a gradation of habitats including a continuous evergreen rainforest, an evergreen rainforest fragment, a continuous semi-deciduous forest and captivity. High throughput microbial 16S ribosomal RNA gene sequencing indicated that diversity, richness and composition of howler GI microbiomes varied with host habitat in relation to diet. Howlers occupying suboptimal habitats consumed less diverse diets and correspondingly had less diverse gut microbiomes. Quantitative real-time PCR also revealed a reduction in the number of genes related to butyrate production and hydrogen metabolism in the microbiomes of howlers occupying suboptimal habitats, which may impact host health.
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http://dx.doi.org/10.1038/ismej.2013.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695285PMC
July 2013

Heavy metal and disinfectant resistance of Listeria monocytogenes from foods and food processing plants.

Appl Environ Microbiol 2012 Oct 27;78(19):6938-45. Epub 2012 Jul 27.

Department of Genomic Sciences, North Carolina State University, Raleigh, North Carolina, USA.

The persistence of Listeria monocytogenes in food processing plants and other ecosystems reflects its ability to adapt to numerous stresses. In this study, we investigated 138 isolates from foods and food processing plants for resistance to the quaternary ammonium disinfectant benzalkonium chloride (BC) and to heavy metals (cadmium and arsenic). We also determined the prevalence of distinct cadmium resistance determinants (cadA1, cadA2, and cadA3) among cadmium-resistant isolates. Most BC-resistant isolates were resistant to cadmium as well. Arsenic resistance was encountered primarily in serotype 4b and was an attribute of most isolates of the serotype 4b epidemic clonal group ECIa. Prevalence of the known cadmium resistance determinants was serotype associated: cadA1 was more common in isolates of serotypes 1/2a and 1/2b than 4b, while cadA2 was more common in those of serotype 4b. A subset (15/77 [19%]) of the cadmium-resistant isolates lacked the known cadmium resistance determinants. Most of these isolates were of serotype 4b and were also resistant to arsenic, suggesting novel determinants that may confer resistance to both cadmium and arsenic in these serotype 4b strains. The findings may reflect previously unrecognized components of the ecological history of different serotypes and clonal groups of L. monocytogenes, including exposures to heavy metals and disinfectants.
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http://dx.doi.org/10.1128/AEM.01553-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3457492PMC
October 2012

Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities.

PLoS One 2010 Nov 12;5(11):e13963. Epub 2010 Nov 12.

The Institute for Genomic Biology, University of Illinois, Urbana, Illinois, United States of America.

Background: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys.

Methodology/principal Findings: We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny.

Conclusion/significance: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013963PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980488PMC
November 2010

Comparative genomics of Gardnerella vaginalis strains reveals substantial differences in metabolic and virulence potential.

PLoS One 2010 Aug 26;5(8):e12411. Epub 2010 Aug 26.

Institute for Genomic Biology, University of Illinois, Urbana, Illinois, USA.

Background: Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9.

Principal Findings: Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species.

Conclusions: Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012411PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928729PMC
August 2010

Conservation of genomic localization and sequence content of Sau3AI-like restriction-modification gene cassettes among Listeria monocytogenes epidemic clone I and selected strains of serotype 1/2a.

Appl Environ Microbiol 2010 Aug 25;76(16):5577-84. Epub 2010 Jun 25.

North Carolina State University, Department of Food Science, Raleigh, North Carolina 27695-7624, USA.

Listeria monocytogenes is a food-borne pathogen with a clonal population structure and apparently limited gene flow between strains of different lineages. Strains of epidemic clone I (ECI) have been responsible for numerous outbreaks and invariably have DNA that is resistant to digestion by Sau3AI, suggesting methylation of cytosine at GATC sites. A putative restriction-modification (RM) gene cassette has been identified in the genome of the ECI strain F2365 and all other tested ECI strains but is absent from other strains of the same serotype (4b). Homologous RM cassettes have not been reported among L. monocytogenes isolates of other serotypes. Furthermore, conclusive evidence for the involvement of this RM cassette in the Sau3AI resistance phenotype of ECI strains has been lacking. In this study, we describe a highly conserved RM cassette in certain strains of serotypes 1/2a and 4a that have Sau3AI-resistant DNA. In these strains the RM cassette was in the same genomic location as in the ECI reference strain F2365. The cassette included a gene encoding a putative recombinase, suggesting insertion via site-specific recombination. Deletion of the RM cassette in the ECI strain F2365 and the serotype 1/2a strain A7 rendered the DNA of both strains susceptible to Sau3AI digestion, providing conclusive evidence that the cassette includes a gene required for methylation of cytosine at GATC sites in both strains. The findings suggest that, in addition to its presence in ECI strains, this RM cassette and the accompanying genomic DNA methylation is also encountered among selected strains of other lineages.
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http://dx.doi.org/10.1128/AEM.00648-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918945PMC
August 2010

Ophthalmomyiasis is not only a problem for rural regions of Eastern Anatolia of Turkey.

Med Sci Monit 2009 Nov;15(11):CS166-8

Department of Parasitology, Faculty of Medicine, Firat University, Elazig, Turkey.

Background: Ophthalmomyiasis externa results from infestation of the conjunctiva by the larval or maggot form of Oestrus ovis. It is common in sheep-farming areas, especially in Mediterranean countries.

Case Report: A 40-year-old man was admitted to the ophthalmology outpatient clinic at State Hospital. He complained of a foreign-body sensation. He was living in a city center in Eastern Anatolia of Turkey. The larvae were removed and antibiotic drops and ointment were given to the patient. The larvae were first-instar Oestrus ovis larvae.

Conclusions: The authors consider ophthalmomyiasis to be not only a problem of rural areas and subsequent examination is very important to ensure that no complications have occurred. It is hoped that this case encourages physicians to be aware of the diagnosis of ophthalmomyiasis externa and its complication and treatment.
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November 2009

Analysis of milk gland structure and function in Glossina morsitans: milk protein production, symbiont populations and fecundity.

J Insect Physiol 2008 Aug 4;54(8):1236-42. Epub 2008 Jul 4.

Yale School of Public Health, Department of Epidemiology and Microbial Diseases, 60 College Street, 606 LEPH New Haven, CT 06510, USA.

A key process in the tsetse reproductive cycle is the transfer of essential nutrients and bacterial symbionts from mother to intrauterine offspring. The tissue mediating this transfer is the milk gland. This work focuses upon the localization and function of two milk proteins (milk gland protein (GmmMGP) and transferrin (GmmTsf)) and the tsetse endosymbionts (Sodalis and Wigglesworthia), in the context of milk gland physiology. Fluorescent in situ hybridization (FISH) and immunohistochemical analysis confirm that the milk gland secretory cells synthesize and secrete milk gland protein and transferrin. Knockdown of gmmmgp by double stranded RNA (dsRNA) mediated RNA interference results in reduction of tsetse fecundity, demonstrating its functional importance in larval nutrition and development. Bacterial species-specific in situ hybridizations of milk gland sections reveal large numbers of Sodalis and Wigglesworthia within the lumen of the milk gland. Sodalis is also localized within the cytoplasm of the secretory cells. Within the lumen, Wigglesworthia localize close to the channels leading to the milk storage reservoir of the milk gland secretory cells. We discuss the significance of the milk gland in larval nutrition and in transmission of symbiotic bacteria to developing offspring.
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http://dx.doi.org/10.1016/j.jinsphys.2008.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613686PMC
August 2008

Epidemic clone I-specific genetic markers in strains of Listeria monocytogenes serotype 4b from foods.

Appl Environ Microbiol 2004 Jul;70(7):4158-64

North Carolina State University, Department of Food Science, Campus Box 7624, Raleigh, NC 27695-7624, USA.

Listeria monocytogenes contamination of ready-to-eat foods has been implicated in numerous outbreaks of food-borne listeriosis. However, the health hazards posed by L. monocytogenes detected in foods may vary, and speculations exist that strains actually implicated in illness may constitute only a fraction of those that contaminate foods. In this study, examination of 34 serogroup 4 (putative or confirmed serotype 4b) isolates of L. monocytogenes obtained from various foods and food-processing environments, without known implication in illness, revealed that many of these strains had methylation of cytosines at GATC sites in the genome, rendering their DNA resistant to digestion by the restriction endonuclease Sau3AI. These strains also harbored a gene cassette with putative restriction-modification system genes as well as other, genomically unlinked genetic markers characteristic of the major epidemic-associated lineage of L. monocytogenes (epidemic clone I), implicated in numerous outbreaks in Europe and North America. This may reflect a relatively high fitness of strains with these genetic markers in foods and food-related environments relative to other serotype 4b strains and may partially account for the repeated involvement of such strains in human food-borne listeriosis.
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http://dx.doi.org/10.1128/AEM.70.7.4158-4164.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC444779PMC
July 2004
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