Purpose

Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.

Methods

We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.

Results

Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).

Conclusions

The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.

Identifying factors associated with condyloma are necessary for prevention efforts. Risk factors for incident condyloma were examined in a cohort of 2487 men from the United States, Brazil, and Mexico and were followed up every 6 months (median, 17.9 months). Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78–40.77]), age (HR, 0.43 [95% CI, .26–.77]; 45–70 vs 18–30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80–17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68–12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

In women, naturally induced anti–human papilloma virus (HPV) serum antibodies are a likely marker of host immune protection against subsequent HPV acquisition and progression to precancerous lesions and cancers. However, it is unclear whether the same is the case in men. In this study, we assessed the risk of incident genital infection and 6-month persistent genital infection with HPV16 in relation to baseline serostatus in a cohort of 2,187 men over a 48-month period. Genital swabs were collected every 6 months and tested for HPV presence. Incidence proportions by serostatus were calculated at each study visit to examine whether potential immune protection attenuated over time. Overall, incidence proportions did not differ statistically between baseline seropositive and seronegative men at any study visit or over the follow-up period. The risk of incident and 6-month persistent infection was not associated with baseline serostatus or baseline serum antibody levels in the cohort. Our findings suggest that baseline HPV seropositivity in men is not associated with reduced risk of subsequent HPV16 acquisition. Thus, prevalent serum antibodies induced by prior infection may not be a suitable marker for subsequent immune protection against genital HPV16 acquisition in men.

Background

The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).

Methods

Genomic DNA was isolated from whole blood, and six VEGF (−2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.

Results

Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).

Conclusion

Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.

Background. Data on the natural history of human papillomavirus (HPV)–related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18–70 years.

Methods. Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction.

Results. Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18–30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%–21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4–19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6–24.2 months).

Conclusions. HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Background

One of the key clinical features of Alzheimer’s disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI.

Methods

The aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a “smart home” equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings.

Results

In P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38–0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68–0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05–0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26–0.45).

Conclusion

In conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention.

Background

Elementary schools are one potential venue for sun protection interventions that reduce childhood sun exposure.

Purpose

To assess Year-2 results from a cluster randomized trial promoting hat use at schools.

Design

Block randomization was used to assign intervention/control status to participating schools. Data were collected from 2006 to 2008 and analyzed in 2007–2010.

Setting/participants

Of the 24 schools in the School District of Hillsborough County, Florida enrolled, fourth-graders were targeted in the first year and followed through their 5th-grade year.

Intervention

Classroom sessions were conducted to improve sun protection knowledge, foster more positive attitudes about hat use, and change the subjective norm of wearing hats when at school.

Main outcome measures

Year-2 outcomes assessed included hat use at school (measured by direct observation), hat use outside of school (measured by self-report) and skin pigmentation and nevi counts (measured for a subgroup of 439 students).

Results

The percentage of students observed wearing hats at control schools remained unchanged during the 2-year period (range 0%–2%) but increased significantly at intervention schools (2% at baseline, 41% at end of Year 1, 19% at end of Year 2; p<0.001 for intervention effect). Measures of skin pigmentation, nevi counts, and self-reported use of hats outside of school did not change during the study period.

Conclusions

This intervention increased use of hats at school through Year 2 but had no measurable effect on skin pigmentation or nevi. Whether school-based interventions can ultimately prevent skin cancer is uncertain.

Primary effusion lymphoma (PEL) is a rare type of lymphoma that arises in the body cavity without detectable masses. It is associated with human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV). Recently, PEL unrelated to viral infection has been reported and it has been termed HHV-8 unrelated primary effusion lymphoma-like lymphoma (HHV-8 unrelated PEL-like lymphoma). Here, we report a case of HHV-8 unrelated PEL-like lymphoma in an 80-year-old woman. Chest X-ray and computed tomography revealed left-sided pleural effusion. Pleural effusion analysis and mediastinoscopic biopsy showed atypical cells that had originated from the B cells. The cells were positive for CD20 and bcl-2, but negative for CD3, CD5, CD21, CD30, CD138, epithelial membrane antigen, and HHV-8. Serological tests for HIV and EBV were negative. Considering the patient's age, further treatments were not performed. She has shown good prognosis without chemotherapy for more than 18 months.

Objective

To develop and perform psychometric testing on an instrument designed to assess cognitive/ emotional responses among men receiving HPV testing.

Methods

Men enrolled in an HPV natural history study (N=139) completed a computer-assisted survey instrument based on Leventhal’s parallel processing/common-sense model. Data were analyzed using SPSS and Mplus.

Results

Reliability analyses resulted in Cronbach α of 0.72 (knowledge), 0.86 (perceived threat), 0.83 (self-efficacy), and 0.55 (response efficacy). A revised measurement model exhibited evidence of construct validity, as indicated by acceptable model fit statistics.

Conclusion

To our knowledge, this is the only validated instrument assessing men’s reactions to an HPV test result.

Objective

The purpose of this study was to determine the prevalence of physician recommendation of human papillomavirus (HPV) vaccination in early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) female patients by physician specialty, and to identify factors associated with recommendation in early adolescents.

Methods

A 38-item survey was conducted April 2009 through August 2009 among a nationally representative random sample of 1,538 Family Physicians, Pediatricians, and Obstetricians and Gynecologists obtained from the American Medical Association Physician Masterfile. A multivariable model was used to assess factors associated with frequency of physician recommendation of HPV vaccination (“always”=76-100% of the time vs. other=0-75%) within the past 12 months.

Results

Completed surveys were received from 1,013 physicians, including 500 Family Physicians, 287 Pediatricians, and 226 Obstetricians and Gynecologists (response rate = 67.8%). Across the specialties, 34.6% of physicians reported they “always” recommend the HPV vaccine to early adolescents, 52.7% to middle adolescents, and 50.2% to late adolescents/young adults. The likelihood of “always” recommending the HPV vaccine was highest among Pediatricians for all age groups (P < .001). Physician specialty, age, ethnicity, reported barriers, and Vaccines for Children provider status were significantly associated with “always” recommending HPV vaccination for early adolescents.

Conclusions

Findings suggest missed clinical opportunities for HPV vaccination, and perceived barriers to vaccination may drive decisions about recommendation. Results suggest the need for age and specialty targeted practice and policy level interventions to increase HPV vaccination among US females.

Purpose

Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI.

Materials and Methods

A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated.

Results

SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI.

Conclusion

SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.

Although the quality of care delivered within the Florida Initiative for Quality Cancer Care practices seems to be high, several components of care were identified that warrant further scrutiny on a systemic level and at individual centers.

Purpose:

The Florida Initiative for Quality Cancer Care (FIQCC) was established to evaluate the quality of cancer care at the regional level across the state of Florida. This study assessed adherence to validated quality indicators in colorectal cancer (CRC) and the variability in adherence by practice site, volume, and patient age.

Methods:

The FIQCC is a consortium of 11 medical oncology practices in Florida. Medical record reviews were conducted for 507 patients diagnosed with CRC and seen as new medical oncology patients in 2006. Thirty-five indicators were evaluated individually and categorized across clinical domains and components of care.

Results:

The mean adherence for 19 of 35 individual indicators was > 85%. Pathology reports were compliant on reporting depth of tumor invasion (96%; range, 86% to 100%), grade (93%; range, 72% to 100%), and status of proximal and distal surgical resection margins (97%; range. 86% to 100%); however, documentation of lymphovascular and perineural invasion did not meet adherence standards (76%; range, 53% to 100% and 39%; range, 5% to 83%, respectively). Among patients with nonmetastatic rectal cancer, documentation of the status of surgical radial margins was consistently low across sites (42%; range, 0% to 100%; P = .19). Documentation of planned treatment regimens for adjuvant chemotherapy was noted in only 58% of eligible patients.

Conclusion:

In this large regional initiative, we found high levels of adherence to more than half of the established quality indicators. Although the quality of care delivered within FIQCC practices seems to be high, several components of care were identified that warrant further scrutiny on both a systemic level and at individual centers.

Male sexual behavior influences the rates of cervical dysplasia and invasive cervical cancer, as well as male human papillomavirus (HPV) infection and disease. Unfortunately, little is known regarding male HPV type distribution by age and across countries. In samples combined from the coronal sulcus, glans penis, shaft, and scrotum of 1,160 men from Brazil, Mexico, and the United States, overall HPV prevalence was 65.2%, with 12.0% oncogenic types only, 20.7% nononcogenic types only, 17.8% both oncogenic and nononcogenic, and 14.7% unclassified infections. Multiple HPV types were detected in 25.7% of study participants. HPV prevalence was higher in Brazil (72.3%) than in the United States (61.3%) and Mexico (61.9%). HPV16 (6.5%), HPV51 (5.3%), and HPV59 (5.3%) were the most commonly detected oncogenic infections, and HPV84 (7.7%), HPV62 (7.3%), and HPV6 (6.6%) were the most commonly detected nononcogenic infections. Overall HPV prevalence was not associated with age. However, significant associations with age were observed when specific categories of HPV, nononcogenic, and unclassified HPV infections were considered. Studies of HPV type distribution among a broad age range of men from multiple countries is needed to fill the information gap internationally with respect to our knowledge of HPV infection in men.

AIM: To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer.

METHODS: The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry.

RESULTS: Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.

CONCLUSION: Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.

Background

Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD).

Methods

Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD.

Results

Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB.

Conclusion

DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

Background

Anticancer therapies that target single signal transduction pathways often fail to prevent proliferation of cancer cells because of overlapping functions and cross-talk between different signaling pathways. Recent research has identified that balanced multi-component therapies might be more efficacious than highly specific single component therapies in certain cases. Ideally, synergistic combinations can provide 1) increased efficacy of the therapeutic effect 2) reduced toxicity as a result of decreased dosage providing equivalent or increased efficacy 3) the avoidance or delayed onset of drug resistance. Therefore, the interest in combinatorial drug discovery based on systems-oriented approaches has been increasing steadily in recent years.

Methodology

Here we describe the development of Combinatorial Drug Assembler (CDA), a genomics and bioinformatics system, whereby using gene expression profiling, multiple signaling pathways are targeted for combinatorial drug discovery. CDA performs expression pattern matching of signaling pathway components to compare genes expressed in an input cell line (or patient sample data), with expression patterns in cell lines treated with different small molecules. Then it detects best pattern matching combinatorial drug pairs across the input gene set-related signaling pathways to detect where gene expression patterns overlap and those predicted drug pairs could likely be applied as combination therapy. We carried out in vitro validations on non-small cell lung cancer cells and triple-negative breast cancer (TNBC) cells. We found two combinatorial drug pairs that showed synergistic effect on lung cancer cells. Furthermore, we also observed that halofantrine and vinblastine were synergistic on TNBC cells.

Conclusions

CDA provides a new way for rational drug combination. Together with phExplorer, CDA also provides functional insights into combinatorial drugs. CDA is freely available at http://cda.i-pharm.org.

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation.

The multiple information sources available may pose a challenge to physicians in providing accurate human papillomavirus (HPV) vaccine information to patients. The purpose of this study was to describe physicians' HPV vaccine information-seeking behaviors and assess if these behaviors differ by physician specialty and sociodemographic characteristics. In 2009, 1,008 Family Physicians (FPs), Pediatricians (Peds), and Obstetric/Gynecologists (OBGYNs) completed a survey to assess their HPV vaccine information-seeking behaviors and vaccination practices. The largest proportion obtained HPV vaccine information from professional organizations (50.0%), followed by the Advisory Council on Immunization Practices (ACIP) (36.0%), and medical conferences (33.1%). Peds and FPs were more likely to obtain vaccine information from the ACIP (p-values < 0.05). OBGYNs, non-White/Caucasian physicians and those aged 40–49 were more likely to obtain vaccine information from internet websites (p-values < 0.05). There is a need for targeted HPV vaccine communication approaches based on sociodemographic and physician specialty characteristics.

Background

The process of drug discovery and development is time-consuming and costly, and the probability of success is low. Therefore, there is rising interest in repositioning existing drugs for new medical indications. When successful, this process reduces the risk of failure and costs associated with de novo drug development. However, in many cases, new indications of existing drugs have been found serendipitously. Thus there is a clear need for establishment of rational methods for drug repositioning.

Results

In this study, we have established a database we call “PharmDB” which integrates data associated with disease indications, drug development, and associated proteins, and known interactions extracted from various established databases. To explore linkages of known drugs to diseases of interest from within PharmDB, we designed the Shared Neighborhood Scoring (SNS) algorithm. And to facilitate exploration of tripartite (Drug-Protein-Disease) network, we developed a graphical data visualization software program called phExplorer, which allows us to browse PharmDB data in an interactive and dynamic manner. We validated this knowledge-based tool kit, by identifying a potential application of a hypertension drug, benzthiazide (TBZT), to induce lung cancer cell death.

Conclusions

By combining PharmDB, an integrated tripartite database, with Shared Neighborhood Scoring (SNS) algorithm, we developed a knowledge platform to rationally identify new indications for known FDA approved drugs, which can be customized to specific projects using manual curation. The data in PharmDB is open access and can be easily explored with phExplorer and accessed via BioMart web service (http://www.i-pharm.org/, http://biomart.i-pharm.org/).

Background

The criteria by Camitta for diagnosis in severe aplastic anemia (SAA) has been used since 1976. However, there has been no attempt to verify the Camitta's criteria, that the survival in patients with SAA may differ by absolute neutrophil count (ANC), platelet count (PLT), and corrected reticulocyte count (CRC), which are components of the Camitta's criteria.

Methods

117 SAA patients diagnosed by the Camitta's criteria were analyzed, retrospectively. Univariate and multivariate analyses were used to evaluate the factors affecting overall survival (OS).

Results

Response by immunosuppressive therapy (IST) or stem cell transplantation (SCT) significantly affected OS (P=0.001). Therefore, we excluded treatment responders for analysis. Finally, 92 SAA patients including treatment non-responders by IST or SCT and conservative care group were analyzed by using univariate and multivariate analyses. The median age of analyzed patients was 54.5 years. Male to female ratio was 1:1. The median follow-up duration was 74.23 months (range, 54.71-93.74 months). The median ANC, PLT, and CRC were 394/µL, 12,000/µL, and 0.39%, respectively. In multivariate analyses, ANC <500/µL or ≥500/µL (P=0.015, HR 2.694, 95% CI: 1.20-6.01) and age (P=0.015, HR 1.022, 95% CI: 1.00-1.04) were the significant factors for OS.

Conclusion

ANC could be an essential, not an optional criterion for diagnosing SAA. This study suggests the possibility that the Camitta's criteria be modified. Studies in large cohorts are needed to transform the Camitta's criteria.

Preclinical and clinical studies have shown that the application of CD105+ mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105+ microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105+/AV− microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105+/AV− microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105+/AV− microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105+/AV− microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032–1.178) after adjusting for other variables. The levels of CD105+/CXCR4+/AV− microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = −0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke.

Background

Few human papillomavirus (HPV) serology studies have evaluated type-specific seroprevalence of vaccine HPV types in men. This study investigates seroprevalence of HPV 6, 11, 16, and 18, and associated risk factors in men residing in three countries (United States, Mexico, and Brazil).

Methods

Data from 1,477 men aged 18 to 70 enrolled in the HPV Infection in Men Study (HIM Study) were analyzed. Serum antibody testing was performed with virus-like particle-based ELISA. Potential risk factors were assessed for individual HPV types by the use of logistic regression.

Results

Overall, HPV-6, 11, 16, and 18 seroprevalence was 14.8%, 17.3%, 11.2%, and 5.8%, respectively. Thirty-four percent of men were seropositive to one or more HPV types. When examined by sexual practice, 31.2% of men who had sex with women, 65.6% of men who had sex with men (MSM), and 59.4% of men who had sex with both men and women (MSMW) were seropositive to one or more HPV types. Seroprevalence increased with age among young-to-middle-aged men with significant upward age trends observed for HPV 11, 16, and 18. Men with multiple lifetime male anal sex partners were 2 to 4 times more likely to be HPV 6 or 11 seropositive and 3 to 11 times more likely to be HPV 16 or 18 seropositive.

Conclusion

Our data indicate that exposures to vaccine HPV types were common in men and highly prevalent among MSM and MSMW.

Impact

Our study provides strong evidence that the practice of same-sex anal intercourse is an independent risk factor for seroprevalence of individual vaccine HPV types. Examination of antibody responses to HPV infections at various anatomic sites in future studies is needed to elaborate on the mechanism.

Background

To better understand the potential ecotoxicological impacts of silver nanoparticles released into freshwater environments, the Daphnia magna 48-hour immobilization test was used.

Methods

The toxicities of silver nitrate, two types of colloidal silver nanoparticles, and a suspension of silver nanoparticles were assessed and compared using standard OECD guidelines. Also, the swimming behavior and visible uptake of the nanoparticles by Daphnia were investigated and compared. The particle suspension and colloids used in the toxicity tests were well-characterized.

Results

The results obtained from the exposure studies showed that the toxicity of all the silver species tested was dose and composition dependent. Plus, the silver nanoparticle powders subsequently suspended in the exposure water were much less toxic than the previously prepared silver nanoparticle colloids, whereas the colloidal silver nanoparticles and AgNO3 were almost similar in terms of mortality. The silver nanoparticles were ingested by the Daphnia and accumulated under the carapace, on the external body surface, and connected to the appendages. All the silver species in this study caused abnormal swimming by the D. magna.

Conclusion

According to the present results, silver nanoparticles should be classified according to GHS (Globally Harmonized System of classification and labeling of chemicals) as "category acute 1" to Daphnia neonates, suggesting that the release of nanosilver into the environment should be carefully considered.

Abstract

Cell therapy promotes brain remodeling and improves functional recovery after various central nervous system disorders, including traumatic brain injury (TBI). We tested the hypothesis that treatment of TBI with intravenous administration of human marrow stromal cells (hMSCs) provides therapeutic benefit in modifying hemodynamic and structural abnormalities, which are detectable by in vivo MRI. hMSCs were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Male Wistar rats (300–350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, approximately 3×106 SPIO-labeled hMSCs) 5 days post-TBI. In vivo MRI measurements consisting of cerebral blood flow (CBF), T2-weighted imaging, and 3D gradient echo imaging were performed for all animals 2 days post-TBI and weekly for 6 weeks. Functional outcome was evaluated with modified neurological severity score and Morris water maze test. Cell engraftment was detected in vivo by 3D MRI and confirmed by double staining. Ventricle and lesion volumetric alterations were measured using T2 maps, and hemodynamic abnormality was tracked by MRI CBF measurements. Our data demonstrate that treatment with hMSCs following TBI diminishes hemodynamic abnormalities by early restoration and preservation of CBF in the brain regions adjacent to and remote from the impact site, and reduces generalized cerebral atrophy, all of which may contribute to the observed improvement of functional outcome.