Miracle-dz/UniFAR-FTUs huggingface dataset:
Bloodstream Infection After Kidney Transplantation: Epidemiology, Microbiology, Associated Risk Factors, and Outcome

Background. Bloodstream infection (BSI) is associated with both relevant morbidity and mortality rates after kidney transplantation. Methods. From January 1, 2000 to January 31, 2006, all episodes of BSI were retrospectively assessed through the review of medical records in two tertiary teaching Hospitals in Sao Paulo, Brazil, where 3308 transplant procedures were performed during this period. Contaminants and polymicrobial infections were excluded. The main objectives of the study were to describe clinical and microbiologic aspects of BSI, as well as risk factors for both BSI and mortality from these infections in kidney transplant patients. Results. BSI was detected in 185 patients, with onset after a median of 235 days after transplantation; 62% occurred after 6 months. The primary source of infection was the urinary tract in 37.8%. The most prevalent pathogen overall was Escherichia coli (30.3%). Risk factors for early acquired BSI (first 6 months after transplantation) were acute rejection, ureteric stent placement, and receiving an organ from a deceased donor. For late BSI (after 6 months), associated risk factors were acute rejection, Charlson Comorbidity Score more than or equal to 3, and receiving an organ from a deceased donor. Risk factors related to 30-day mortality were Acute Physiology and Chronic Health Evaluation II Score more than or equal to 20, shock, and respiratory failure. Conclusions. BSI is most frequently a consequence of urinary tract infection, with a high prevalence of gram-negative bacilli. Severity of disease was the main determinant of 30-day mortality after BSI, and based on the knowledge of risk factors, some interventions are suggested for reducing the rate of BSI after transplantation.
Predicted 30‐year protection after vaccination with an aluminum‐free virosomal hepatitis A vaccine

Few studies have examined the duration of protection following vaccination against hepatitis A virus (HAV) with currently licensed HAV vaccines. This study explored the long‐term immunogenicity in individuals vaccinated with the virosomal hepatitis A virus, Epaxal®. Adult volunteers (N = 130) previously enrolled into four different studies between 1992 and 1994 and who had completed a 0/12‐month immunization regimen (primary and booster dose) were asked to participate in this follow‐up study. Yearly anti‐HAV titers up to 6 years following booster vaccination, and then once 9–11 years after booster were measured using two assays, Enzygnost® and AxSYM® HAVAB 2.0. Based on the Enzygnost® assay, the seroprotection rate 9–11 years after booster was 100%, with a geometric mean concentration (GMC) of anti‐HAV antibodies of 526 mIU/ml. Females had markedly higher GMCs than males (741 mIU/ml vs. 332 mIU/ml). Using an anti‐HAV cut‐off titer of ≥10 mIU/ml, a linear mixed mathematical model predicted a median duration of protection of 52.1 years. A duration of protection ≥35.7 years was predicted for 95% of subjects. A more stringent cut‐off of ≥20 mIU/ml shortened the median predicted duration of protection to 45.0 years. In conclusion, a two‐dose Epaxal® vaccination regimen confers in healthy adults a real‐time protection of at least 9–11 years; this protection is predicted to last at least 30 years in over 95% of individuals. Further studies are necessary to assess the real duration of seroprotection and whether an additional booster is necessary later. J. Med. Virol. 82:1629–1634, 2010. 2010 Wiley‐Liss, Inc.
Comparison of the effects on glycaemic control and β‐cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel‐group trial (the CONFIDENCE study)

Progressive β‐cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on β‐cell‐protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on β‐cell function of three antihyperglycaemic agents that have a β‐cell‐protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes.
The emerging role of microRNAs in cardiovascular disease

Cardiovascular disease remains the most prevalent cause of human morbidity and mortality in ageing Western societies. Basic and translational scientific efforts have focused on the development and improvement of diagnostic and therapeutic strategies to limit the burden of associated diseases, such as stroke and myocardial infarction, and diabetes mellitus and arterial hypertension. Progress in molecular medicine and biology has unravelled a complex epigenetic and post‐transcriptional gene‐regulating machinery in humans which may limit disease development. An increasing number of attractive molecular strategies, which use the potential of modulating noncoding RNAs, have surfaced over the last decade. Currently, the most extensively studied gene‐regulating RNA subspecies are microRNAs, which have been shown to adjust the translational output of coding transcripts by enforcing their degradation and inhibiting their translation into protein. Key findings indicate that microRNAs act as crucial regulators in the majority of human pathologies. Thus, recent research has focused on detecting and modulating microRNAs for therapeutic and biomarker purposes. This review focuses on main and repeated discoveries regarding the role and the therapeutic and biomarker feasibility of microRNAs during cardiovascular disease development and exacerbation.
Rapid discrimination of oseltamivir‐resistant 275Y and ‐susceptible 275H substitutions in the neuraminidase gene of pandemic influenza A/H1N1 2009 virus by duplex one‐step RT‐PCR assay†

Pandemic influenza A/H1N1 2009 (A/H1N1pdm) virus caused significant outbreaks worldwide last year (2009). A number of oseltamivir‐resistant A/H1N1pdm viruses possessing an H275Y substitution in the neuraminidase (NA) protein were reported sporadically in several countries, including Japan, but they were sensitive to zanamivir and did not spread in the community. In this study, to monitor rapidly and simply oseltamivir‐resistant A/H1N1pdm viruses possessing H275Y, a duplex one‐step RT‐PCR assay (H275Y RT‐PCR assay) was developed based on an endpoint genotyping analysis method. H275Y RT‐PCR assay evaluated using several subtypes/types of influenza A and B viruses and other respiratory pathogenic viruses and shown to have high sensitivity and high specificity. Forty‐four clinical specimens were tested after RNA purification using the H275Y RT‐PCR assay, resulting in one clinical specimen being found to contain a virus possessing the H275Y mutation. Seventy‐three clinical isolates were then tested with the H275Y assay by using clinical isolates in the cultured supernatants of cells directly, without RNA purification, and the results were consistent with the NA sequencing. Since the H275Y RT‐PCR assay could detect the H275Y mutation in clinical isolates without RNA purification, as well as a H275Y mutated virus in clinical specimens after RNA purification, the assay was considered a powerful tool for surveillance screening of oseltamivir‐resistant A/H1N1pdm virus activity. J. Med. Virol. 83:1121–1127, 2011. © 2011 Wiley‐Liss, Inc.
MANUAL FOR THE IDENTIFICATION OF MEDICAL BACTERIA

Cowan and the late Steel, whose untimely death at the age of 34 occurred between completion of the manuscript and the proof stage of the book, have prepared a valuable manual for the identification of medically important bacteria in pure culture. The first 43 pages (Chapters 1-5) deal with classification and nomenclature; importance of pure cultures; characterization of isolates; and theory and practice of bacterial identification. Chapters 6-8 (pages 44-91) contain the most valuable parts of the volume, namely, tables aiding in the identification of gram-positive, gramnegative, and miscellaneous bacteria. These tables are preceded by brief descriptions of the microorganisms. The volume is concluded with appendixes describing culture media, staining reagents and methods, and various tests aiding in the identification of bacteria, and with a valuable list of more than 500 references. Although the authors, with a few exceptions, did not intend to discuss serology, it is clear that serologic methods frequently aid in identification and further characterization of unknown cultures of medical importance. For example, such methods are indispensable for the identification of enteropathogenic Escherichia coli, and helpful in other instances. Comments on these serologic tests in a new edition would strengthen the volume. This manual will be of great help to workers in diagnostic bacteriology laboratories. ERWIN NETER
Innovations in User Involvement: The Development and Evaluation of a Preparatory Training Package for Service User Representatives

Background: Research has highlighted that poor preparation and/or lack of appropriate skills may be a barrier to effective and credible implementation of User Involvement (UI) in mental health services. Aims: To describe the development and evaluation of a unique training package delivered to members of a service user reference group to enable them to contribute to staff training aimed at improving attitudes towards borderline personality disorder. Method: Semi-structured individual interviews were conducted with six participants who had received the training package. Results: An analysis of participants’ comments revealed six key themes: personal and professional gains, importance of team work, satisfaction with teaching, lack of organisation, difficulties with communication and recruitment issues. All participants rated the training package very highly, but inappropriate recruitment of user representatives and a lack of funding and subsequent consistent practical support were cited as barriers to effective UI. Conclusions: Careful selection and training of user representatives is vital to maximise the efficacy of UI, and ensure that it is a positive experience for user representatives. Further robust comparative research is required to demonstrate the usefulness of UI, and inform evidence-based practice.
Antiviral efficacy of combination therapy with entecavir and adefovir for entecavir/lamivudine‐resistant hepatitis B virus with or without adefovir resistance

There is little clinical information on the management of hepatitis B virus (HBV) that is resistant to multiple drugs including entecavir (ETV). The present retrospective cohort study assessed the antiviral efficacy of ETV/adefovir dipivoxil (ADV) combination therapy for ETV‐resistant HBV with prior lamivudine (LAM) resistance, and either with or without previous ADV resistance. The cumulative probability of achieving a virological response (undetectable serum HBV DNA) was compared by Kaplan–Meier analysis and the Breslow method. Seventeen patients with ETV‐resistant HBV who were treated with ETV/ADV combination therapy for at least 6 months at a tertiary care center, were included; seven had dual resistance to ETV and LAM [ADV‐r(−) group] and 10 had triple resistance to ETV, LAM, and ADV [ADV‐r(+) group]. The median follow‐up period was 9 months (range, 6–23). A virological response was noted in seven patients after a median of 3 months (range, 3–12) of treatment; five in the ADV‐r(−) group and two in the ADV‐r(+) group. The cumulative probability of a virological response was significantly higher in the ADV‐r(−) group than in the ADV‐r(+) group (6 months cumulative probability, 57.1% vs. 11.1%). In conclusion, ETV/ADV combination therapy led to virological responses in five of seven patients with resistance to ETV and LAM, but a significantly poorer response in patients with prior ADV resistance than in those without prior ADV resistance. Therefore, ETV/ADV combination therapy could be a useful therapeutic option for ETV‐ and LAM‐resistant HBV without prior ADV resistance. J. Med. Virol. 84:424–430, 2012. © 2011 Wiley Periodicals, Inc.
Trial Registration and Declaration of Registration by Authors of Randomized Controlled Trials

Background. Trial registration was introduced to reduce research bias by promoting trial transparency and accountability. We aimed to evaluate the frequency of, and factors associated with, trial registration and declaration of trial registration. Methods. We selected all randomized controlled trials in kidney transplantation published between October 2005 and December 2010 and determined whether a trial was registered and whether a trial declared their registration in subsequent trial reports. Results. Of 307 eligible trials identified, 24% (74/307) were registered, and of those, 59% (44/74) contained trial registration details within at least one trial report. Trial registration was more likely for trials published more than once, in later years or reported in journals that followed the International Committee of Medical Journal Editors guidelines. Trial registration was less likely for trials that did not declare their funding sources. Registered trials were more likely to declare registration details in related reports if published in later years or in a journal that followed International Committee of Medical Journal Editors guidelines. Trials that did not declare their funding sources were less likely to declare registration details. Conclusions. Although still suboptimal, the situation is improving over time, with both trial registration and declaration of registration details more likely in later years.
Occurrence of human bocaviruses and parvovirus 4 in solid tissues

Human bocaviruses 1‐4 (HBoV1‐4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2‐4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1‐4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1‐4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species‐specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus‐like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2‐4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. J. Med. Virol. 84: 1267–1273, 2012. © 2012 Wiley Periodicals, Inc.
Islet Graft Survival and Function: Concomitant Culture and Transplantation With Vascular Endothelial Cells in Diabetic Rats

Background. Human islet transplantation is a great potential therapy for type I diabetes. To investigate islet graft survival and function, we recently showed the improved effects after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. Methods. ECs were isolated, and the viability of isolated islets was assessed in two groups (standard culture group and co-culture group with ECs). Then streptozotocin-induced diabetic rats were divided into four groups before islet transplantation as follows: group A with infusion of islet grafts; group B with combined vascular ECs and islet grafts; groups C and D as controls with single ECs infusion and phosphate-buffered saline injection, respectively. Blood glucose and insulin concentrations were measured daily. Expression of vascular endothelial growth factor was investigated by immunohistochemical staining. The mean microvascular density was also calculated. Results. More than 90% of acridine orange-propidium iodide staining positive islets demonstrated normal morphology while co-cultured with ECs for 7 days. Compared with standard control, insulin release assays showed a significantly higher simulation index in co-culture group except for the first day (P<0.05). After transplantation, there was a significant difference in concentrations of blood glucose and insulin among these groups after 3 days (P<0.05). The mean microvascular density in co-culture group was significantly higher than that in single islet group (P=0.04). Conclusion. Co-culture with ECs in vitro could improve the survival and function of isolated rat islet, and co-transplantation of islets with ECs could effectively prolong the islet graft survival in diabetic rats.
A single nucleotide polymorphism in IL28B affects viral evolution of hepatitis C quasispecies after pegylated interferon and ribavirin therapy

Interleukin‐28B (IL28B) polymorphisms are associated with viral response to peginterferon and ribavirin (RBV) in chronic hepatitis C (HCV). Their recognition represents a breakthrough in the understanding of the role of the host in viral eradication. How these polymorphisms determine viral eradication is unknown. The IL‐28B variants are hypothesized to have a differential impact on HCV quasispecies evolution during treatment with pegylated interferon (PEG‐IFN) and RBV. In this study, HCV RNA levels were measured at early time points in 33 naïve genotype 1 hepatitis C patients and clonal analysis of the entire NS5A region was performed on sera from baseline and Day 7. Site rs12979860 polymorphisms were determined by direct sequencing of PCR products and classified into CC, CT, and TT and were identified in 13, 11, and 9 patients, respectively. The CC polymorphism more commonly was seen in Whites versus Blacks [12/21 (57%) vs. 1/12 (8%), P = 0.009] and HIV‐infected versus mono‐infected [13/25 (52%) vs. 0/8 (0%), P = 0.009]. Patients with CC and non‐CC had similar baseline viral loads. More patients with the CC polymorphism had amino acid substitutions in NS5A compared to non‐CC patients. Despite similar baseline viral diversity, by Day 7, significantly more patients with CC had higher non‐synonymous substitution values compared to non‐CC (P = 0.02). Chronic hepatitis C patients with the CC IL28B polymorphism have a higher number of amino acid substitutions in the NS5A region and early viral evolution due to greater interferon induced selective pressure during this critical period of treatment. J. Med. Virol. 84:1913–1919, 2012. © 2012 Wiley Periodicals, Inc.
Hepatitis C virus NS2 protease inhibits host cell antiviral response by inhibiting IKKε and TBK1 functions

Hepatitis C virus (HCV) encodes for several proteins that can interfere with host cell signaling and antiviral response. Previously, serine protease NS3/4A was shown to block host cell interferon (IFN) production by proteolytic cleavage of MAVS and TRIF, the adaptor molecules of the RIG‐I and TLR3 signaling pathways, respectively. This study shows that another HCV protease, NS2 can interfere efficiently with cytokine gene expression. NS2 and its proteolytically inactive mutant forms were able to inhibit type I and type III IFN, CCL5 and CXCL10 gene promoters activated by Sendai virus infection. However, the CXCL8 gene promoter was not inhibited by NS2. In addition, constitutively active RIG‐I (ΔRIG‐I), MAVS, TRIF, IKKε, and TBK1‐induced activation of IFN‐β promoter was inhibited by NS2. Cotransfection experiments with IKKε or TBK1 together with interferon regulatory factor 3 (IRF3) and HCV expression constructs revealed that NS2 in a dose‐dependent manner inhibited IKKε and especially TBK1‐induced IRF3 phosphorylation. GST pull‐down experiments with GST‐NS2 and in vitro‐translated and cell‐expressed IKKε and TBK1 demonstrated direct physical interactions of the kinases with NS2. Further evidence that the IKKε/TBK1 kinase complex is the target for NS2 was obtained from the observation that the constitutively active form of IRF3 (IRF3‐5D) activated readily IFN‐β promoter in the presence of NS2. The present study identified HCV NS2 as a potent interferon antagonist, and describes an explanation of how NS2 downregulates the major signaling pathways involved in the development of host innate antiviral responses. J. Med. Virol. 85:71–82, 2012. © 2012 Wiley Periodicals, Inc.
Detection of multiple viral and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: A pilot prospective study†

Few studies have evaluated the contribution of multiple virus and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease. This study estimated the burden of multiple viral and bacterial respiratory infections in moderate to very severe chronic obstructive pulmonary disease patients that were prospectively followed‐up during a 12‐month pilot study. Clinical data were collected monthly and sputum was collected at the time of each acute exacerbation event. Classical culture techniques for bacteria and multiplex polymerase chain reaction (PCR) and microarray detection assays were performed to identify viral and atypical bacterial pathogens in the sputum. Overall, 51 patients were included and 45 acute exacerbation events were investigated clinically and microbiologically. Among the 45 acute exacerbation events, 44% had evidence of viral infection involving human rhinovirus (HRV) and metapneumovirus (hMPV) in 20% and 18%, respectively. Intracellular bacteria were not found in sputum by PCR. Common bacterial pathogens were identified in 42% of acute exacerbation patients, most frequently Branhamella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae. Viral or virus and bacteria co‐infections were detected in 27% of acute exacerbation events (n = 12) with HRV and hMPV involved in 92% of cases. Patients with co‐infections did not present greater clinical severity scores at exacerbation and more recurrence of acute exacerbation events at 3 and 6 months than those with single infections (P > 0.4). These results suggest that HRV and hMPV may be contributors or cofactors of AECOPD. These findings indicate that viral or virus and bacterial co‐infections do not impact significantly on the clinical severity of acute exacerbation of chronic obstructive pulmonary disease and recurrence at 3 and 6 months. J. Med. Virol. 85:866–873, 2013. © 2013 Wiley Periodicals, Inc.