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Find video protocols related to scientific articles indexed in Pubmed.
Prevalence of Chromosomally Integrated Human Herpesvirus 6 in Patients with Human Herpesvirus 6-Central Nervous System Dysfunction.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-17-2014
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We identified 37 hematopoietic cell transplantation recipients with human herpesvirus 6 (HHV-6) central nervous system dysfunction and tested donors-recipient pairs for chromosomally integrated HHV-6 (ciHHV-6). One patient had ciHHV-6A with possible HHV-6A reactivation and encephalitis. There was no ciHHV-6 enrichment in this group, but larger studies are needed to determine if patients with ciHHV-6 are at increased risk for HHV-6-associated diseases or other complications.
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Interactions of endoplasmic reticulum and mitochondria Ca(2+) stores with capacitative calcium entry.
Metab Brain Dis
PUBLISHED: 03-28-2014
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Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine deficiency in vitro and in rodents is a useful model of this reduction. Thiamine interacts with cellular calcium stores. To directly test the relevance of the thiamine dependent changes to dynamic processes in AD, the interactions must be studied in cells from patients with AD. These studies employed fibroblasts. Mitochondrial dysfunction including reductions in thiamine dependent enzymes and abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts from Alzheimer's Disease (AD) patients. Bombesin-releasable calcium stores (BRCS) from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients with AD bearing a presenilin-1 (PS-1) mutation and in control fibroblasts treated with oxidants. ER calcium regulates calcium entry into the cell through capacitative calcium entry (CCE), which is reduced in fibroblasts and neurons from mice bearing PS-1 mutations. Under physiological conditions, mitochondria and ER play important and interactive roles in the regulation of Ca(2+) homeostasis. Thus, the interactions of mitochondria and oxidants with CCE were tested. Inhibition of ER Ca(2+)-ATPase by cyclopiazonic acid (CPA) stimulates CCE. CPA-induced CCE was diminished by inhibition of mitochondrial Ca(2+) export (-60 %) or import (-40 %). Different aspects of mitochondrial Ca(2+) coupled to CPA-induced-CCE were sensitive to select oxidants. The effects were very different when CCE was examined in the presence of InsP3, a physiological regulator of ER calcium release, and subsequent CCE. CCE under these conditions was only mildly reduced (20-25 %) by inhibition of mitochondrial Ca(2+) export, and inhibition of mitochondrial Ca(2+) uptake exaggerated CCE (+53 %). However, t-BHP reversed both abnormalities. The results suggest that in the presence of InsP3, mitochondria buffer the local Ca(2+) released from ER following rapid activation of InsP3R and serve as a negative feedback to the CCE. The results suggest that mitochondrial Ca(2+) modifies the depletion and refilling mechanism of ER Ca(2+) stores.
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Oral HHV-8 replication among women in Mombasa, Kenya.
J. Med. Virol.
PUBLISHED: 03-11-2014
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Human herpesvirus-8 (HHV-8) replication in the oropharynx may play an important role in HHV-8 transmission and contribute to the development of Kaposi sarcoma (KS) in some individuals. Studies in the United States and Europe report high rates of HHV-8 DNA detection in saliva of HHV-8 infected men, but little is known about the natural history of HHV-8 among persons in sub-Saharan Africa, where prevalence of HHV-8 infection and KS is greatest. To address this gap, this study evaluated oral HHV-8 replication in a cohort of 40 HHV-8 seropositive Kenyan women. Study clinicians collected daily oral swabs from participants for up to 30 consecutive days, and swab samples were tested for HHV-8 DNA using quantitative, real-time polymerase chain reaction. HHV-8 was detected at least once in 27 (68%) participants, and the overall shedding rate was 23%. On days with HHV-8 detection, mean HHV-8 quantity was 4.5?log10 ?copies/ml. Among HIV-infected women, CD4 count ?500?cells/mm(3) versus <500?cells/mm(3) was associated with higher HHV-8 copy number (4.8?log10 ?copies/ml vs. 3.4?log10 ?copies/ml; coef 1.2 [95% CI, 0.5-1.9]; P?=?0.001) and a higher HHV-8 shedding rate (49% vs.12%; RR, 4.2 [95% CI, 0.8-21.4]; P?=?0.08). No other factors were associated with HHV-8 shedding rate or copy number. The study demonstrates high rates and quantity of HHV-8 in the oropharynx of HHV-8 seropositive African women. These findings support the observation that oral replication is an essential feature of HHV-8 infection, with likely implications for HHV-8 transmission and KS pathogenesis.
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Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR.
Clin. Chem.
PUBLISHED: 03-04-2014
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Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests.
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Reduced human herpesvirus-8 oropharyngeal shedding associated with protease inhibitor-based antiretroviral therapy.
J. Clin. Virol.
PUBLISHED: 02-21-2014
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Human herpesvirus 8 (HHV-8) replication increases the risk of Kaposi sarcoma (KS). Highly-active antiretroviral therapy (HAART) reduces the incidence of KS, and regimens that contain protease inhibitors (PIs) may be particularly effective.
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Virologic and immunologic evidence of multifocal genital herpes simplex virus 2 infection.
J. Virol.
PUBLISHED: 02-19-2014
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Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract.
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Accelerated suppression of primary Epstein-Barr virus infection in HIV-infected infants initiating lopinavir/ritonavir-based versus nevirapine-based combination antiretroviral therapy.
Clin. Infect. Dis.
PUBLISHED: 02-18-2014
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We compared primary Epstein-Barr virus (EBV) infection and suppression between Kenyan human immunodeficiency virus-infected infants starting nevirapine-based vs lopinavir/ritonavir-based antiretroviral regimens. Although the rate of EBV infection was similar between groups, infants receiving lopinavir/ritonavir suppressed EBV more rapidly. Our findings suggest that specific antiretrovirals may potentially impact the risk of future EBV-associated malignancies.
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In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease.
Mol Ther Nucleic Acids
PUBLISHED: 02-06-2014
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Following acute infection, herpes simplex virus (HSV) establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they do not prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks in latent HSV genomes by rare-cutting endonucleases, leading to mutagenesis of essential viral genes. We tested this approach in an in vitro HSV latency model using the engineered homing endonuclease (HE) HSV1m5, which recognizes a sequence in the HSV-1 gene UL19, encoding the virion protein VP5. Coexpression of the 3'-exonuclease Trex2 with HEs increased HE-mediated mutagenesis frequencies up to sixfold. Following HSV1m5/Trex2 delivery with adeno-associated viral (AAV) vectors, the target site was mutated in latent HSV genomes with no detectable cell toxicity. Importantly, HSV production by latently infected cells after reactivation was decreased after HSV1m5/Trex2 exposure. Exposure to histone deacetylase inhibitors prior to HSV1m5/Trex2 treatment increased mutagenesis frequencies of latent HSV genomes another two- to fivefold, suggesting that chromatin modification may be a useful adjunct to gene-targeting approaches. These results support the continuing development of HEs and other nucleases (ZFNs, TALENs, CRISPRs) for cure of chronic viral infections.Molecular Therapy-Nucleic Acids (2014) 3, e1; doi:10.1038/mtna.2013.75; published online 4 February 2014.
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Frequent genital HSV-2 shedding among women during labor in Soweto, South Africa.
Infect Dis Obstet Gynecol
PUBLISHED: 01-21-2014
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Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor.
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Helicase-primase inhibitor pritelivir for HSV-2 infection.
N. Engl. J. Med.
PUBLISHED: 01-17-2014
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Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection.
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Video-assisted thoracoscopic surgery for postoperative recurrent primary spontaneous pneumothorax.
J Thorac Dis
PUBLISHED: 01-06-2014
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Postoperative recurrent primary spontaneous pneumothorax (PSP) is a troublesome complication and an important issue to be discussed. This study is to determine whether Re-video assisted thoracoscopic surgery (VATS) should be performed for postoperative recurrent PSP (PORP).
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Quantitation of cytomegalovirus DNA load in dried blood spots correlates well with plasma viral load.
J. Clin. Microbiol.
PUBLISHED: 05-15-2013
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An assay to accurately quantitate cytomegalovirus (CMV) load in finger-stick-collected dried blood spots (DBS) could potentially be useful for field studies or for analyzing patient self-collected specimens. We therefore assessed CMV DNA load in paired venipuncture-collected plasma samples and finger-stick DBS, using a previously validated quantitative PCR assay. Assay variability, sensitivity, and changes in viral load during antiviral therapy in finger-stick DBS were compared to the reference plasma quantitative PCR assay, using 106 prospectively collected pairs of finger-stick DBS and plasma samples from 35 solid-organ transplant (SOT) patients. The DBS assay showed good agreement with the reference plasma viral load assay on the log10 scale (Pearson correlation coefficient, 0.92; P < 0.001). The 95% limit of detection of the DBS assay was estimated at 2,700 plasma copies/ml (675 plasma IU/ml). In 94% (76/81) of paired DBS and plasma samples above the limit of detection, the difference in CMV load was <1 log10. CMV viral load changes during antiviral treatment were comparable in plasma and DBS. We conclude that finger-stick DBS provides a convenient sample type for quantitation of CMV load that correlates well with plasma levels. Future studies to optimize and evaluate this methodology for patient self-collected samples are warranted.
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Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir-resistant strains to the helicase-primase inhibitor pritelivir.
Antiviral Res.
PUBLISHED: 05-08-2013
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Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were tested for sensitivity to the helicase-primase inhibitor, pritelivir (AIC316, BAY 57-1293) by plaque-reduction assay. All isolates, which were collected prior to any clinical use of primase-helicase inhibitors, were sensitive and showed mean EC50 values of 0.026 and 0.029?M for HSV-1 and HSV-2, respectively. Furthermore, several laboratory-selected acyclovir-resistant HSV mutants were also sensitive to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in general population before it is introduced and broadly used to treat HSV infection. The data also validate pritelivir as an appropriate therapy for nucleoside-resistant HSV infections.
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An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia.
J. Clin. Virol.
PUBLISHED: 04-24-2013
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Additional drugs are needed for the treatment of cytomegalovirus (CMV) infection. Artesunate is an antimalarial drug that has activity against CMV in vitro and in a rodent model. Only a small number of case reports are available describing the clinical effects of artesunate on CMV infection, and these yielded inconsistent results.
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High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-02-2013
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Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding.
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Clinical and virologic manifestations of primary Epstein-Barr virus (EBV) infection in Kenyan infants born to HIV-infected women.
J. Infect. Dis.
PUBLISHED: 03-14-2013
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Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)-associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy.
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Population-based assessment of kaposi sarcoma-associated herpesvirus DNA in plasma among Ugandans.
J. Med. Virol.
PUBLISHED: 03-07-2013
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Risk of Kaposi sarcoma (KS) is linked to detection of Kaposi sarcoma-associated herpesvirus (KSHV) DNA in plasma, but little is known about the prevalence and risk factors for plasma KSHV DNA detection among the general population where KS is endemic. Correlates of KSHV plasma detection were investigated in a population-based sample of adult Ugandans (15-59 years) who participated in an HIV/AIDS serobehavioral survey in 2004/2005. KSHV DNA was measured in plasma of 1,080 KSHV seropositive and 356 KSHV seronegative persons using polymerase chain reaction (PCR). KSHV DNA in plasma was detected in 157 (8.7%) persons; of these 149 (95%) were KSHV seropositive and 8 (5%) were seronegative. Detection of KSHV DNA in plasma was significantly associated with male sex (P?
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Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model.
J. Surg. Res.
PUBLISHED: 02-02-2013
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Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.
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A novel DNA vaccine technology conveying protection against a lethal herpes simplex viral challenge in mice.
PLoS ONE
PUBLISHED: 01-01-2013
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While there are a number of licensed veterinary DNA vaccines, to date, none have been licensed for use in humans. Here, we demonstrate that a novel technology designed to enhance the immunogenicity of DNA vaccines protects against lethal herpes simplex virus 2 (HSV-2) challenge in a murine model. Polynucleotides were modified by use of a codon optimization algorithm designed to enhance immune responses, and the addition of an ubiquitin-encoding sequence to target the antigen to the proteasome for processing and to enhance cytotoxic T cell responses. We show that a mixture of these codon-optimized ubiquitinated and non-ubiquitinated constructs encoding the same viral envelope protein, glycoprotein D, induced both B and T cell responses, and could protect against lethal viral challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a vector suitable for use in humans, also provided a high level of protection against the establishment of ganglionic latency, an important correlate of HSV reactivation and candidate endpoint for vaccines to proceed to clinical trials.
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Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract.
Elife
PUBLISHED: 01-01-2013
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Herpes simplex virus-2 (HSV-2) is shed episodically, leading to occasional genital ulcers and efficient transmission. The biology explaining highly variable shedding patterns, in an infected person over time, is poorly understood. We sampled the genital tract for HSV DNA at several time intervals and concurrently at multiple sites, and derived a spatial mathematical model to characterize dynamics of HSV-2 reactivation. The model reproduced heterogeneity in shedding episode duration and viral production, and predicted rapid early viral expansion, rapid late decay, and wide spatial dispersion of HSV replication during episodes. In simulations, HSV-2 spread locally within single ulcers to thousands of epithelial cells in <12 hr, but host immune responses eliminated infected cells in <24 hr; secondary ulcers formed following spatial propagation of cell-free HSV-2, allowing for episode prolongation. We conclude that HSV-2 infection is characterized by extremely rapid virological growth and containment at multiple contemporaneous sites within genital epithelium. DOI:http://dx.doi.org/10.7554/eLife.00288.001.
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Detection of adeno-associated virus viremia in hematopoietic cell transplant recipients.
J. Infect. Dis.
PUBLISHED: 10-17-2011
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Adeno-associated virus (AAV) is widely considered to be nonpathogenic, but the clinical epidemiology of this virus is limited. By use of polymerase chain reaction assays, we investigated the incidence and clinical significance of AAV viremia in a population of consecutive recipients of a hematopoietic cell transplant (HCT). Four (2.8%) of 145 patients developed AAV viremia after HCT. Viremia was low level and transient in all patients. Two patients were admitted to the hospital and died in proximity to AAV viremia (<7 weeks between diagnosis and death); however, AAV was not detected in tissue specimens obtained at autopsy. Thus, AAV does not appear to play a pathogenic role in organ-specific illness, even in a highly immunocompromised population.
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Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men.
J. Med. Virol.
PUBLISHED: 08-13-2011
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Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually infected men enrolled in three previous clinical trials of valacyclovir and famciclovir for HIV-1 and/or HSV-2 suppression. Fifty-eight participants contributed 6,036 swabs. HHV-8 was detected in 1,128 (19%) of 6,036 swabs, including 618 (21%) of 2,992 on placebo, 323 (15%) of 2,221 on valacyclovir, and 187 (23%) of 823 on famciclovir. After adjusting for baseline HIV viral load and highly active antiretroviral therapy (HAART) use, an 18% reduction in HHV-8 shedding frequency (IRR 0.822; P?=?0.011) was found in participants on valacyclovir and a 30% reduction (IRR 0.700; P?
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Comparison of needlescopic and conventional video-assisted thoracic surgery for primary spontaneous pneumothorax.
Minim Invasive Ther Allied Technol
PUBLISHED: 05-16-2011
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Whether the outcome of primary spontaneous pneumothorax (PSP) when treated with needlescopic video-assisted thoracic surgery is positive is still under scrutiny. The present study was conducted to compare the needlescopic approach with the conventional approach. One-hundred and six patients with primary spontaneous pneumothorax who had undergone needlescopic video-assisted thoracic surgery (NVATS) between May 2006 and August 2008 were reviewed. Their age, gender, smoking status, BMI, side of attack, operative indications, operative time, intraoperative blood loss, postoperative length of stay, postoperative pain in visual analog scale (VAS), postoperative recurrence and follow-up period were recorded. These data were compared with those of 89 patients with PSP who had undergone conventional video-assisted thoracic surgery (CVATS) between June 2002 and April 2006. The operative time was shorter (NVATS: 82.36 ± 35.58 min, CVATS: 99.78 ± 35.74 min; p = 0.008) and intraoperative blood loss was less (NVATS: 16.67 ± 25.90 ml, CVATS: 24.36 ± 26.86 ml; p = 0.04) for the NVATS group. The postoperative pain in VAS was significantly less in NVATS. No major complication or mortality was found in either group. For treatment of primary spontaneous pneumothorax, NVATS is a safe and effective option. Further, it has the added benefit of less pain and improved cosmetics.
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Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection.
JAMA
PUBLISHED: 04-14-2011
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Since herpes simplex virus type 2 (HSV-2) antibody tests have become commercially available, an increasing number of persons have learned that they have genital herpes through serologic testing. The course of natural history of HSV-2 in asymptomatic, seropositive persons is uncertain.
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Aortobronchial fistula after esophagectomy for esophageal cancer -- a very rare complication.
Kaohsiung J. Med. Sci.
PUBLISHED: 04-13-2011
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Most aorto-respiratory fistulas are related to aortic pathology or procedures, but fistula formation after esophageal resection has never been reported in the literature. We are now reporting a case of hemoptysis that occurred after esophagectomy for locally advanced esophageal cancer. Aortobronchial fistula was detected by computed tomography scan. The patient was finally saved by emergency surgery-Dacron graft interposition of the descending thoracic aorta. There was no malignant cell in the postoperative specimen of the fistula. The erosion of the ligaclips (Johnson & Johnson) might be responsible for the aortobronchial fistula formation. For esophageal surgery, avoidance of trauma to aortic wall and careful using of ligaclips are important to circumvent this complication.
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Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 03-23-2011
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A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.
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Cytomegalovirus viremia as a risk factor for mortality prior to antiretroviral therapy among HIV-infected gold miners in South Africa.
PLoS ONE
PUBLISHED: 03-22-2011
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Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV.
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HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients.
Blood
PUBLISHED: 03-09-2011
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Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.
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Congenital cytomegalovirus infection in pediatric hearing loss.
Arch. Otolaryngol. Head Neck Surg.
PUBLISHED: 01-19-2011
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To compare the prevalence of congenital cytomegalovirus (CMV) infection in Washington State in children with hearing loss (HL) and the general population and to compare the characteristics of HL in children with and without congenital CMV infection.
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Genital HSV detection among HIV-1-infected pregnant women in labor.
Infect Dis Obstet Gynecol
PUBLISHED: 01-13-2011
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To compare genital HSV shedding among HIV-positive and HIV-negative women.
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Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.
J. Infect. Dis.
PUBLISHED: 12-09-2010
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Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking.
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Thiamine and oxidants interact to modify cellular calcium stores.
Neurochem. Res.
PUBLISHED: 07-30-2010
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Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimers disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant. The current experiments first tested directly whether thiamin could act as an antioxidant, and then examined the physiological relevance of the antioxidant properties on oxidant sensitive, calcium dependent processes that are altered in AD. The first group of experiments examined whether thiamin could diminish reactive oxygen species (ROS) or reactive nitrogen species (RNS) produced by two very divergent paradigms. Dose response curves determined the concentrations of t-butyl-hydroperoxide (t-BHP) (ROS production) or 3-morpholinosydnonimine ((SIN-1) (RNS production) to induce oxidative stress within cells. Concentrations of thiamine that reduced the RNS in cells did not diminish the ROS. The second group of experiments tested whether thiamine alters oxidant sensitive aspects of calcium regulation including endoplasmic reticulum (ER) calcium stores and capacitative calcium entry (CCE). Thiamin diminished ER calcium considerably, but did not alter CCE. Thiamine did not alter the actions of ROS on ER calcium or CCE. On the other hand, thiamine diminished the effect of RNS on CCE. These data are consistent with thiamine diminishing the actions of the RNS, but not ROS, on physiological targets. Thus, both experimental approaches suggest that thiamine selectively alters RNS. Additional experiments are required to determine whether diminished thiamine availability promotes oxidative stress in AD or whether the oxidative stress in AD brain diminishes thiamine availability to thiamine dependent processes.
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Rapidly cleared episodes of oral and anogenital herpes simplex virus shedding in HIV-infected adults.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-10-2010
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To determine whether rapidly cleared episodes of herpes simplex virus (HSV) reactivation occur in HIV-infected adults.
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The lytic activation of KSHV during keratinocyte differentiation is dependent upon a suprabasal position, the loss of integrin engagement, and calcium, but not the interaction of cadherins.
Virology
PUBLISHED: 06-15-2010
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We previously found that KSHV (HHV-8) lytic activation occurs during differentiation of oral keratinocytes in organotypic raft cultures. To further investigate the spatial and temporal aspects of KSHV lytic activation and the roles of integrins, cadherins, and calcium, we used rKSHV.219-infected primary oral keratinocytes in submerged, suspension, and direct suprabasal plating, models of differentiation. We found that early keratinocyte differentiation did not activate lytic KSHV in cells attached to a substratum, with activation only occurring in suprabasal cells. Temporally, KSHV lytic expression occurred between the expression of early and late differentiation markers. Keratinocytes differentiated in suspension culture, which mimics substratum loss that occurs with stratification, activated lytic KSHV. This lytic activation was inhibited by integrin engagement, showing that integrins are a control point for KSHV reactivation. A role for cadherins was not found. Elevated extracellular calcium was necessary, but not sufficient, for lytic activation.
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Factors predicting the hospital mortality of patients with corrosive gastrointestinal injuries receiving esophagogastrectomy in the acute stage.
World J Surg
PUBLISHED: 06-01-2010
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The aim of this study was to identify the preoperative factors that affect the survival of patients who undergo esophagogastrectomy after corrosive ingestion, using analysis of their physiological condition, associated diseases, physical examination, and laboratory data.
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Rapid polymerase chain reaction assay to detect herpes simplex virus in the genital tract of women in labor.
Obstet Gynecol
PUBLISHED: 05-27-2010
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To develop a rapid quantitative real-time polymerase chain reaction (PCR) to detect herpes simplex virus (HSV) in the genital secretions of women that may be used in labor.
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Radical resection or chemoradiotherapy for cervical esophageal cancer?
World J Surg
PUBLISHED: 04-24-2010
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The prognosis and quality of life (QOL) for those with cervical esophageal cancer is extremely poor, and chemoradiotherapy remains the mainstay treatment. During the past few years, our surgical teams has implemented a more aggressive and radical resection: total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach. This study compares the results of chemoradiotherapy and that of the aforementioned surgical approach.
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Frequent detection of human adenovirus from the lower gastrointestinal tract in men who have sex with men.
PLoS ONE
PUBLISHED: 02-04-2010
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The association between baseline seropositivity to human adenovirus (HAdV) type 5 and increased HIV acquisition in the Step HIV Vaccine Study has raised questions concerning frequency of acquired and/or persistent Adenovirus infections among adults at high risk of HIV-1 infection.
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Overlapping reactivations of herpes simplex virus type 2 in the genital and perianal mucosa.
J. Infect. Dis.
PUBLISHED: 01-22-2010
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Genital shedding of herpes simplex virus (HSV) type 2 occurs frequently. Anatomic patterns of genital HSV-2 reactivation have not been intensively studied.
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Evasion of the mucosal innate immune system by herpes simplex virus type 2.
J. Virol.
PUBLISHED: 09-30-2009
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Understanding the mechanisms by which herpes simplex virus (HSV) evades host immune defenses is critical to defining new approaches for therapy and prevention. We performed transcriptional analyses and immunocytochemistry on sequential biopsy specimens of lesional tissue from the acute through the posthealing phases of recurrent mucocutaneous HSV-2 infection. Histological analysis of these biopsy specimens during the acute stage revealed a massive infiltration of T cells, as well as monocytes/macrophages, a large amount of myeloid, and a small number of plasmacytoid dendritic cells, in the dermis of these lesional biopsy specimens. Type I interferon (IFN-beta and IFN-alpha) was poorly expressed and gamma IFN (IFN-gamma) potently induced during time periods in which we detected abundant amounts of HSV-2 antigens and HSV-2 RNA. IFN-stimulated genes were also markedly upregulated, with expression patterns that more closely matched those in primary human fibroblasts treated by IFN-gamma than those in fibroblasts treated by IFN-beta. Transcriptional arrays of the same lesional biopsy sites during healing and at 2 and 4 weeks posthealing revealed no HSV nucleic acids or antigen; however, there was persistent expression of IFN-gamma, with very low levels of IFN-beta and IFN-alpha. The findings of extremely low levels of IFN-alpha and IFN-beta, despite the presence of a large number of cells capable of synthesizing these substances, suggest a potent alteration in host defense during HSV-2 infection in vivo. HSV-2s blockade of the innate immune systems production of type I IFN may be a major factor in allowing the virus to break through host mucosal defenses.
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A prospective comparison of transthoracic and transhiatal resection for esophageal carcinoma in Asians.
Hepatogastroenterology
PUBLISHED: 07-23-2009
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Transthoracic and transhiatal esophagectomy are two common procedures for esophageal cancer resection. Prospective studies comparing the two methods in Asian people are few. In addition, the data comparing their effects on the quality of life are lacking.
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Is prophylactic treatment of contralateral blebs in patients with primary spontaneous pneumothorax indicated?
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 06-10-2009
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More than 50% of patients with primary spontaneous pneumothorax have contralateral blebs/bullae, and about a quarter will develop a contralateral pneumothorax. The purpose of this prospective study was to determine the need for elective treatment of asymptomatic contralateral blebs/bullae in patients presenting with primary spontaneous pneumothorax.
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Vaccine prevention of maternal cytomegalovirus infection.
N. Engl. J. Med.
PUBLISHED: 03-20-2009
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Congenital infection with cytomegalovirus (CMV) is an important cause of hearing, cognitive, and motor impairments in newborns.
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Impact of HIV infection and Kaposi sarcoma on human herpesvirus-8 mucosal replication and dissemination in Uganda.
PLoS ONE
PUBLISHED: 01-20-2009
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Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.
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Needlescopic video-assisted thoracic surgery for primary spontaneous pneumothorax.
Minim Invasive Ther Allied Technol
PUBLISHED: 01-01-2009
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Minimally invasive surgery is the current trend of approach in various fields. Since May 2006, our team has started implementing needlescopic video-assisted thoracic surgery as the standard surgical treatment for primary spontaneous pneumothorax. During a seventeen-month period, 62 consecutive patients with primary spontaneous pneumothorax were operated on. The ages, sex ratio, operative times, blood loss, postoperative pain in visual analog scale (VAS), length of stay and hospital costs were recorded and compared with that of another 62 consecutive patients who received conventional video-assisted thoracic surgery between July 2004 and April 2006. Only the postoperative pain in VAS was significantly lower in the needlescopic video-assisted thoracic surgery group; the rest remained the same. Also the wounds were almost undetectable in the needlescopic video-assisted thoracic surgery patients. There were no major complications, mortality or recurrence in either group. Needlescopic video-assisted thoracic surgery is a high-tech technique which provides safety, effectiveness, economy and outcome comparable to that of conventional techniques. It is also associated with less pain and better cosmetics.
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Changes in the soluble mucosal immune environment during genital herpes outbreaks.
J. Acquir. Immune Defic. Syndr.
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Genital tract secretions provide variable inhibitory activity against herpes simplex virus (HSV) ex vivo. We hypothesize that the anti-HSV activity may prevent the spread of virus from the more commonly affected sites, such as the external genitalia, to the upper genital tract.
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HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
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Human herpesvirus 6 (HHV-6) reactivation has been associated with acute graft-versus-host-disease (aGVHD), cytomegalovirus reactivation, and mortality after allogeneic hematopoietic cell transplantation (HCT), but previous studies have yielded inconsistent results. We performed a large prospective study of allogeneic HCT recipients in order to more definitively define the relationships between HHV-6 and these important outcomes. Plasma specimens were collected prospectively from 315 allogeneic HCT recipients and tested for HHV-6 DNA at baseline and twice weekly for 12 weeks. Cox proportional hazards models were used to evaluate the time-dependent associations between HHV-6 reactivation and the targeted outcomes. HHV-6 was detected in 111 of 315 patients (35%) at a median of 20 days after HCT. HHV-6 reactivation was associated with subsequent cytomegalovirus reactivation (adjusted hazard ratio [aHR], 1.9; 95% confidence interval [CI], 1.3-2.8; P = .002). High-level HHV-6 (>1,000 HHV-6 DNA copies/mL) was associated with subsequent grades II to IV aGVHD (aHR, 2.4; 95% CI, 1.60-3.6; P < .001). High-level HHV-6 reactivation was also associated with nonrelapse mortality (aHR, 2.7; 95% CI, 1.2-6.3; P = .02). HHV-6 reactivation was independently and quantitatively associated with increased risk of subsequent cytomegalovirus reactivation, aGVHD, and mortality after HCT. A randomized antiviral trial is warranted to establish causality between HHV-6 and these endpoints and to determine if reducing HHV-6 reactivation will improve outcome after HCT.
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Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection.
J. Gen. Virol.
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The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD(50) inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80?% survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40?% of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine.
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Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients.
Biol. Blood Marrow Transplant.
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Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R- HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R- HCT recipients.
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Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials.
Lancet
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Skin and mucosal herpes simplex virus type 2 (HSV-2) shedding predominantly occurs in short subclinical episodes. We assessed whether standard-dose or high-dose antiviral therapy reduces the frequency of such shedding.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.