HIV/Sexually Transmitted Infection Risk Behaviors in Delinquent Youth with Psychiatric Disorders: A Longitudinal Study

ERIC Educational Resources Information Center

Elkington, Katherine; Teplin, Linda A.; Mericle, Amy A.; Welty, Leah J.; Romero, Erin G.; Abram, Karen M.

2008-01-01

The effect of psychiatric disorders on human immunodeficiency virus/sexually transmitted infection (HIV/STI) risk behaviors in juvenile justice youths is examined. Prevalence, persistence and prediction are addressed among four mutually exclusive diagnostic groups and results show a high prevalence rate of many HIV/STI sexual risk behaviors that…

Flying over an infected landscape: Distribution of highly pathogenic avian influenza H5N1 risk in South Asia and satellite tracking of wild waterfowl

USGS Publications Warehouse

Gilbert, Marius; Newman, Scott H.; Takekawa, John Y.; Loth, Leo; Biradar, Chandrashekhar; Prosser, Diann J.; Balachandran, Sivananinthaperumal; Rao, Mandava Venkata Subba; Mundkur, Taej; Yan, Baoping; Xing, Zhi; Hou, Yuansheng; Batbayar, Nyambayar; Tseveenmayadag, Natsagdorj; Hogerwerf, Lenny; Slingenbergh, Jan; Xiao, Xiangming

2010-01-01

Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May,June,July 2009 in China(Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl.

Variants of human papillomavirus type 16 predispose toward persistent infection

PubMed Central

Zhang, Lei; Liao, Hong; Yang, Binlie; Geffre, Christopher P; Zhang, Ai; Zhou, Aizhi; Cao, Huimin; Wang, Jieru; Zhang, Zhenbo; Zheng, Wenxin

2015-01-01

A cohort study of 292 Chinese women was conducted to determine the relationship between human papillomavirus (HPV) type 16 variants and persistent viral infection. Enrolled patients were HPV16 positive and had both normal cytology and histology. Flow-through hybridization and gene chip technology was used to identify the HPV type. A PCR sequencing assay was performed to find HPV16 E2, E6 and E7 gene variants. The associations between these variants and HPV16 persistent infection was analyzed by Fisher’s exact test. It was found that the variants T178G, T350G and A442C in the E6 gene, as well as C3158A and G3248A variants in the E2 gene were associated with persistent HPV16 infection. No link was observed between E7 variants and persistent viral infection. Our findings suggest that detection of specific HPV variants would help identify patients who are at high risk for viral persistence and development of cervical neoplasia. PMID:26339417

Natural history of anal human papillomavirus infection in heterosexual women and risks associated with persistence.

PubMed

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-03-01

Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Natural History of Anal Human Papillomavirus Infection in Heterosexual Women and Risks Associated With Persistence

PubMed Central

Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen

2014-01-01

Background. Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Methods. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Results. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. Conclusions. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence. PMID:24368624

Human biomonitoring reference values for some non-persistent chemicals in blood and urine derived from the Canadian Health Measures Survey 2009-2013.

PubMed

Khoury, Cheryl; Werry, Kate; Haines, Douglas; Walker, Mike; Malowany, Morie

2018-05-01

The Canadian Health Measures Survey collects nationally representative human biomonitoring data on a suite of chemicals and their metabolites, including many non-persistent chemicals. Data has been collected on non-persistent chemicals, including acrylamide, chlorophenols, environmental phenols and triclocarban, organophosphate insecticides, phthalates, polycyclic aromatic hydrocarbon, pyrethroid insecticides, and volatile organic compounds from 2009 to 2013. Using a systematic approach building on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry, we derive human biomonitoring reference values (RV 95 s) for these classes of non-persistent chemicals in blood and urine for the general Canadian population. RV 95 s were derived for biomarkers of non-persistent chemicals with widespread detection in Canadians (>66% detection rate). Samples with urinary creatinine levels outside the recommended range of 0.3-3.0 μg/L were excluded. Reference populations were constructed by applying smoking and fasting as exclusion criteria where appropriate. Age and sex were evaluated as possible partitioning criteria and separate RV 95 s were derived for sub-populations in cases where partitioning was deemed necessary. Reference values were derived for 40 biomarkers and represent the first set of RV 95 s for non-persistent chemicals in the general Canadian population. These values provide a measure of the upper margin of background exposure in the general population and can be compared against individual and population human biomonitoring data. RV 95 s can be used to by public health officials to identify individuals with high exposures, and by risk assessors and risk managers to identify atypical exposures or subpopulations with elevated exposures. Crown Copyright © 2018. Published by Elsevier GmbH. All rights reserved.

Spatial analysis on human brucellosis incidence in mainland China: 2004–2010

PubMed Central

Zhang, Junhui; Yin, Fei; Zhang, Tao; Yang, Chao; Zhang, Xingyu; Feng, Zijian; Li, Xiaosong

2014-01-01

Objectives China has experienced a sharply increasing rate of human brucellosis in recent years. Effective spatial monitoring of human brucellosis incidence is very important for successful implementation of control and prevention programmes. The purpose of this paper is to apply exploratory spatial data analysis (ESDA) methods and the empirical Bayes (EB) smoothing technique to monitor county-level incidence rates for human brucellosis in mainland China from 2004 to 2010 by examining spatial patterns. Methods ESDA methods were used to characterise spatial patterns of EB smoothed incidence rates for human brucellosis based on county-level data obtained from the China Information System for Disease Control and Prevention (CISDCP) in mainland China from 2004 to 2010. Results EB smoothed incidence rates for human brucellosis were spatially dependent during 2004–2010. The local Moran test identified significantly high-risk clusters of human brucellosis (all p values <0.01), which persisted during the 7-year study period. High-risk counties were centred in the Inner Mongolia Autonomous Region and other Northern provinces (ie, Hebei, Shanxi, Jilin and Heilongjiang provinces) around the border with the Inner Mongolia Autonomous Region where animal husbandry was highly developed. The number of high-risk counties increased from 25 in 2004 to 54 in 2010. Conclusions ESDA methods and the EB smoothing technique can assist public health officials in identifying high-risk areas. Allocating more resources to high-risk areas is an effective way to reduce human brucellosis incidence. PMID:24713215

Prophylaxis of Human Hydrophobia in South Korea

PubMed Central

2014-01-01

Domestic human hydrophobia has not been reported since the one case of 2004 in South Korea, but still a few animal rabies occur persistently since the reemerging stage of rabies from 1993. The government has made efforts to control animal rabies in many aspects, but whether prophylactic strategy for human hydrophobia is performed adequately is in question. The rate of proper post-exposure prophylaxis for animal bite case in 'high-risk region' of rabies is very low with 20% between 2011 and 2013. The National Animal Bite Patient Surveillance targeting 'high-risk region' is missing out animal bite cases who visit directly to hospitals in 'suspect-risk region' of rabies. Little data seems to exist for pre-exposure prophylaxis of domestic hydrophobia. Danger of reoccurrence of human hydrophobia always remain in South Korea. The medical personnel needs to have greater interest on the matter and the government strengthen the management system. PMID:25298903

Hazardous air pollutants in industrial area of Mumbai - India.

PubMed

Srivastava, Anjali; Som, Dipanjali

2007-09-01

Hazardous Air Pollutants (HAPs) have a potential to be distributed into different component of environment with varying persistence. In the current study fourteen HAPs have been quantified in the air using TO-17 method in an industrial area of Mumbai. The distribution of these HAPs in different environmental compartments have been calculated using multi media mass balance model, TaPL3, along with long range transport potential and persistence. Results show that most of the target compounds partition mostly in air. Phenol and trifluralin, partition predominantly into soil while ethyl benzene and xylene partition predominantly into vegetation compartment. Naphthalene has the highest persistence followed by ethyl benzene, xylene and 1,1,1 trihloro ethane. Long range transport potential is maximum for 1,1,1 trichloroethane. Assessment of human health risk in terms of non-carcinogenic hazard and carcinogenic risk due to exposure to HAPs. have been estimated for industrial workers and residents in the study area considering all possible exposure routes using the output from TaPL3 model. The overall carcinogenic risk for residents and workers are estimated as high as unity along with very high hazard potential.

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

PubMed Central

Téllez, Luis; Michelli, Elvia; Mendoza, José Andrés; Vielma, Silvana; Noguera, María-Eugenia; Callejas, Diana; Cavazza, María; Correnti, María

2015-01-01

Cervical lesions have been associated with infection by high-risk human papilloma virus (high-risk HPV). In 409 women aged >15 years high-risk HPV lesions were identified. In a cohort of this population persistent infection was compared with cytological, colposcopic, and histological lesions. Cervical scrapes were taken and DNA was isolated. HPV was detected by PCR in the E6/E7 region. Genotyping was performed by PCR nested multiple E6/E7. HPV was detected in a 37.40% (153/409), high-risk HPV in 86% (153/178), HPV18 46.64% (83/178), HPV16 34.28% (61/178). Among these 53.93% (96/178) were multiple infections, and HPV18/16 (30/96) was the most frequent 31.25%. The cytology showed changes in 15% of positive patients. A 49.67% in women positive for HPV infection showed abnormalities in the colposcopic study, a relationship that turned out to be statistically significant ( p < 0.0019 test χ2). Among all 85% of the women were younger than 45 years of age. Fifty-seven patients were evaluated 15 months after the base study, with initial prevalence of morbidity 49.12% (28/57) and at the end 10.53% (6/57), showing in 89.29% (25/28) negative for HR-HPV infection, 10.34% (3/28) showed persistence of infection, 17.54% (10/57) presented cytological alterations, with 80% of positivity for HPV, and a regression of 100% (10/10) of the previously identified lesions. With colposcopy, 50% (14/28) presented alterations related to HPV, of these 85.71% (12/14) showed regression of such an alteration. The cumulative incidence for HPV was 10.34% (3/29). The incidence rate was 4.23% (3/71), which is equal to 4.23 new cases of HPV infection per 100 people, per year of follow-up. In conclusion, the present work shows a high frequency of infection by high-risk HPV, with predominance of HPV18 and 16 and in general for multiple infections. Colposcopy was better predictor than the Pap smear for infection. The follow-up study revealed a low percentage of persistent infection, and a high frequency of negativity for viral infection, high regression of cytological and colposcopic lesions, a low cumulative and incidence rate similar to that reported by other Latin American countries and higher than the European countries. PMID:26557877

Persistent high-risk human papillomavirus (HPV) infections as surrogate endpoints of progressive cervical disease. Potential new endpoint for efficacy studies with new-generation (non-HPV 16/18) prophylactic HPV vaccines.

PubMed

Syrjänen, K

2011-01-01

Recent data indicate that persistent HR-HPV infections represent a significantly increased risk of developing incident high-grade CIN and cervical cancer. Accordingly, 6-month (6M+) or 12-month (12M+) type-specific persistence of HR-HPV have been proposed as powerful surrogates of progressive disease. Because of substantial practical impact in future HPV vaccine trials using non-HPV 16/18 vaccines, studies on HR-HPV persistence as a surrogate endpoint of progressive CIN have been subject to a comprehensive meta-analyses recently. The present communication was solicited to bring this important and timely topic to the awareness of the readers, in a format consisting of a review of the recent literature, supplemented with the author's own experience from different studies. Based on a large number of relevant studies, there remains little doubt that persistence of HR-HPV for 6+ or 12+ months is associated with a significantly increased risk of developing incident high-grade CIN. However, some data also disclosed several important issues that need to be carefully considered and/or adequately resolved before adopting 6M+ or 12M+ HR-HPV persistence as a surrogate of progressive disease. These include i) definitions of HPV persistence, ii) HPV detection techniques and iii) testing intervals and iv) length of follow-up, as well as v) diagnosis of the surrogate endpoints, and vi) other study characteristics, including vii) the type of reference category used in calculating the risk estimates. All these issues are critically discussed in the present communication. Of major impact seems to be the reference category used to calculate these risk estimates, as evident from the NIS-LAMS cohort. Taken together, it is suggested that in all future studies using the 6M+ or 12M+ HR-HPV persistence as a surrogate endpoint of progressive disease, a "gold standard" should be used in calculating the risk estimates. In addition to deciding, 1) whether to use 6M+ or 12M+ persistence criteria, and 2) cytological, histological or combined surrogate endpoints (SIL, CIN1, CIN2, CIN/SIL), one should 3) use exclusively the HPV negative reference group in calculating the risk estimates for viral persistence endpoints. This is supported by the data from the recent meta-analysis as well as from the author's combined NIS-LAMS cohort, both implicating that the most consistent association to progressive disease is obtained when women with persistent HR-HPV are compared with HPV-negative women. It is the conviction of this author that the two other reference categories (HPV transient and HPV mixed outcome) are far too heterogeneous and subject to potential misclassifications to give consistent and reproducible risk estimates for HR-HPV persistence as a surrogate endpoint of progressive CIN.

Presence of high-risk human papillomavirus genotype and human immunodeficiency virus DNA in anal high-grade and low-grade squamous intraepithelial lesions.

PubMed

Shiramizu, Bruce; Liang, Chin-Yuan; Agsalda-Garcia, Melissa; Nagata, Ian; Milne, Cris; Zhu, Xuemei; Killeen, Jeffrey; Berry, J Michael; Goodman, Marc T

2013-01-01

Human immunodeficiency virus type 1 (HIV)-infected individuals are at risk for anal cancer, which is caused by human papillomavirus (HPV). The relationship between HIV and HPV that leads to anal cancer remains unclear. Recent data, however, suggest that the continued persistence of HIV DNA in patients treated with combined antiretroviral therapy leads to progression of HIV disease and other HIV-associated complications. Therefore, we investigated the relationship among anal low- and high-grade squamous intraepithelial lesions (LGSIL/HGSIL), high-risk HPV genotypes, and high HIV DNA copy numbers. Anal cytology specimens were assayed for HPV genotype and HIV DNA copy number. High-risk HPV genotypes (odds ratio OR: 3.73; 95% confidence interval CI: 1.08-12.91; p=0.04) and high HIV DNA copy numbers (OR(per 100 HIV DNA copies): 1.13; 95% CI: 1.01-1.27, p=0.04) were both associated with LGSIL/HGSIL. When considering both high-risk HPV genotypes and HIV DNA copy numbers in predicting LGSIL/HGSIL, HIV DNA copy number was significant (OR(per 100 HIV DNA copies): 1.09; 95% CI: 0.96-1.23, p=0.04) but not high-risk HPV genotypes (OR: 2.30, p=0.28), which did not change when adjusted for nadir CD4 cell count and HIV RNA levels. The findings warrant further investigation of HIV DNA and its relationship with HPV in LGSIL/HGSIL pathogenesis.

Risk assessment strategies as nanomaterials transition into commercial applications

NASA Astrophysics Data System (ADS)

Olson, Mira S.; Gurian, Patrick L.

2012-03-01

Commercial applications of nanomaterials are rapidly emerging in the marketplace. The environmental and human health risks of many nanomaterials remain unknown, and prioritizing how to efficiently assess their risks is essential. As nanomaterials are incorporated into a broader range of commercial products, their potential for environmental release and human exposure not only increases, but also becomes more difficult to model accurately. Emphasis may first be placed on estimating potential environmental exposure based on pertinent physical properties of the nanomaterials. Given that the greatest potential for global environmental impacts results from nanomaterials that are both persistent and toxic, this paper advocates screening first for persistence since it is easier to assess than toxicity. For materials that show potential for persistence, a higher burden of proof of their non-toxicity is suggested before they enter the commercial marketplace whereas a lower burden of proof may be acceptable for nanomaterials that are less persistent.

Solid waste containing persistent organic pollutants in Serbia: From precautionary measures to the final treatment (case study).

PubMed

Stevanovic-Carapina, Hristina; Milic, Jelena; Curcic, Marijana; Randjelovic, Jasminka; Krinulovic, Katarina; Jovovic, Aleksandar; Brnjas, Zvonko

2016-07-01

Sustainable solid waste management needs more dedicated attention in respect of environmental and human health protection. Solid waste containing persistent organic pollutants is of special concern, since persistent organic pollutants are persistent, toxic and of high risk to human health and the environment. The objective of this investigation was to identify critical points in the Serbian system of solid waste and persistent organic pollutants management, to assure the life cycle management of persistent organic pollutants and products containing these chemicals, including prevention and final destruction. Data were collected from the Serbian competent authorities, and led us to identify preventive actions for solid waste management that should reduce or minimise release of persistent organic pollutants into the environment, and to propose actions necessary for persistent organic pollutants solid waste. The adverse impact of persistent organic pollutants is multidimensional. Owing to the lack of treatment or disposal plants for hazardous waste in Serbia, the only option at the moment to manage persistent organic pollutants waste is to keep it in temporary storage and when conditions are created (primarily financial), such waste should be exported for destruction in hazardous waste incinerators. Meanwhile, it needs to be assured that any persistent organic pollutants management activity does not negatively impact recycling flows or disturb progress towards a more circular economy in Serbia. © The Author(s) 2016.

Day 3 thyroglobulin ≤ 1 ng/ml after recombinant human TSH just prior to radioactive iodine is predictive of low risk for persistent/recurrent disease in patients with papillary thyroid carcinoma.

PubMed

Rosario, Pedro W; Siman, Thássio Leonardo; Calsolari, Maria R

2015-05-01

We evaluated the negative predictive value (NPV) of thyroglobulin obtained 24 h after the second recombinant human TSH (rhTSH) ampoule (Tg-D3), before ablation with (131)I, for persistent/recurrent disease (PRD) in low/intermediate risk patients with papillary thyroid carcinoma. One hundred and one patients with Tg-D3 ≤ 1 ng/ml without anti-Tg antibodies (TgAb) were selected. Post-therapy whole-body scanning was negative for metastases in 98 (97 %) patients, and three patients showed discrete ectopic cervical uptake, but no corresponding disease was detected by neck ultrasound or computed tomography. One year after ablation, 98 (97 %) patients were free of the disease. Three patients had stimulated Tg >1 ng/ml, but no metastases were detected by the imaging methods. During follow-up (median 50 months), tumor recurrence was observed in only one patient. Thus, the NPV of Tg-D3 ≤ 1 ng/ml for PRD was 99 %. Among the 101 patients with Tg-D3 ≤ 1 ng/ml, Tg obtained 48 h after ablation (Tg-D5) continued to be ≤ 1 ng/ml in 56, and 45 had Tg-D5 >1 ng/ml. None of these 45 patients had PRD. In conclusion, Tg-D3 ≤ 1 ng/ml had a high NPV for PRD in patients without TgAb or known persistent disease and who are not at high risk. In these patients, Tg-D5 >1 ng/ml is more likely to reflect actinic damage to the remnant thyroid tissue rather than persistence of significant normal or tumor tissue.

The EVVA Cohort Study: Anal and Cervical Type-Specific Human Papillomavirus Prevalence, Persistence, and Cytologic Findings in Women Living With HIV.

PubMed

de Pokomandy, Alexandra; Kaufman, Elaina; de Castro, Christina; Mayrand, Marie-Hélène; Burchell, Ann N; Klein, Marina; Charest, Louise; Auger, Manon; Rodrigues-Coutlée, Sophie; Coutlée, François

2017-08-15

The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

PubMed

Molloy, M; Comer, R; Rogers, P; Dowling, M; Meskell, P; Asbury, K; O'Leary, M

2016-11-01

To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis.

PubMed

Yeo-Teh, Nicole S L; Ito, Yoshiaki; Jha, Sudhakar

2018-06-08

Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and E7 achieve persistent expression. The most well-studied cellular targets of the viral oncogenes E6 and E7 are p53 and pRb, respectively. However, recent research has demonstrated the ability of these two viral factors to target many more cellular factors, including proteins which regulate epigenetic marks and splicing changes in the cell. These have the ability to exert a global change, which eventually culminates to uncontrolled proliferation and carcinogenesis.

Improving the risk assessment of lipophilic persistent environmental chemicals in breast milk

EPA Science Inventory

BACKGROUND: A breastfeeding infant’s intake of persistent organic pollutants (POPs) may be much greater than his/her mother’s average daily POP exposure. In many cases, current human health risk assessment methods do not account for differences between maternal and infant POP exp...

Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases.

PubMed

Ruzzin, Jérôme

2012-04-20

Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.

Host control of human papillomavirus infection and disease.

PubMed

Doorbar, John

2018-02-01

Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

Toxins produced in cyanobacterial water blooms – toxicity and risks

PubMed Central

Bláha, Luděk; Babica, Pavel; Maršálek, Blahoslav

2009-01-01

Cyanobacterial blooms in freshwaters represent a major ecological and human health problem worldwide. This paper briefly summarizes information on major cyanobacterial toxins (hepatotoxins, neurotoxins etc.) with special attention to microcystins-cyclic heptapeptides with high acute and chronic toxicities. Besides discussion of human health risks, microcystin ecotoxicology and consequent ecological risks are also highlighted. Although significant research attention has been paid to microcystins, cyanobacteria produce a wide range of currently unknown toxins, which will require research attention. Further research should also address possible additive, synergistic or antagonistic effects among different classes of cyanobacterial metabolites, as well as interactions with other toxic stressors such as metals or persistent organic pollutants. PMID:21217843

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

PubMed

Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

2011-09-21

Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

Cutaneous human papillomaviruses persist on healthy skin.

PubMed

Hazard, Kristina; Karlsson, Anna; Andersson, Kristin; Ekberg, Henrik; Dillner, Joakim; Forslund, Ola

2007-01-01

Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.

Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection

PubMed Central

Vriend, Henrike J; Bogaards, Johannes A; van Bergen, Jan E A M; Brink, Antoinette A T P; van den Broek, Ingrid V F; Hoebe, Christian J P A; King, Audrey J; van der Sande, Marianne A B; Wolffs, Petra F G; de Melker, Hester E

2015-01-01

We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16–29 years-old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates were stratified for chlamydia positivity at follow-up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range: 11–12). Differences in 1-year HPV persistence rates between chlamydia -infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69–1.96] and 1.84 [95% CI: 1.36–2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type-specific acquisition and persistence. PMID:26194784

Persistence of an incident human papillomavirus infection and timing of cervical lesions in previously unexposed young women.

PubMed

Trottier, Helen; Mahmud, Salaheddin M; Lindsay, Lisa; Jenkins, David; Quint, Wim; Wieting, Susan L; Schuind, Anne; Franco, Eduardo L

2009-03-01

We analyzed data from a cohort of 553 women enrolled in the placebo arm of a randomized controlled trial of the human papillomavirus (HPV) 16/18 vaccine to study the timing of the occurrence of squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN) following incident HPV infection and its relation to persistence of the infection. At entry, women were cytologically negative, HPV 16/18 seronegative, and high-risk HPV (HR-HPV) DNA negative. Cervicovaginal samples were initially collected at 3-month and cervical samples at 6-month intervals. We estimated the mean time to SIL/CIN, relative risks of SIL/CIN following incident HPV, and odds ratios between persistent HPV and SIL/CIN. The mean time for SIL/CIN detection was 43.3 [95% confidence interval (95% CI), 36.4-50.1] and 46.4 (95% CI, 42.0-50.7) months from first infection with HPV 16/18 and other HR-HPVs, respectively. Relative risks of SIL/CIN following incident HPV infection were 66.2 (95% CI, 14.9-295.1) for HPV 16/18 and 50.9 (95% CI, 11.5-225.4) for other HR-HPVs. The odds ratios of SIL/CIN for persistent HPV 16/18 infection, defined as a minimum of two and three (6 monthly) visits, were, respectively, 169.0 (95% CI, 37.2-768.6) and 169.1 (95% CI, 31.5-907.4). The majority of women with cervical infection with HPV 16/18 lasting >6 months (33 of 51, 65%) developed SIL and/or CIN. These analyses provide the first actuarial estimate of mean time between incident HR-HPV infection in previously uninfected women and onset of cervical lesion development. Persistent HR-HPV infection, particularly HPV 16/18, is a strong predictor of cervical lesion risk and potentially a reliable end point for clinical HPV research.

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression

PubMed Central

Vryzas, Dimos; Chatzaki, Ekaterini; Koch, Isabel; Soutschek, Erwin; Boecher, Oliver; Tsertanidou, Athena; Maglaveras, Nikolaos; Jansen-Duerr, Pidder; Agorastos, Theodoros

2018-01-01

Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping (MPG), and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95% confidence intervals (CI): 1.365–2.332, p < 0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women. PMID:29385075

Molecular epidemiology, cancer-related symptoms, and cytokines pathway

PubMed Central

Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay

2012-01-01

The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalised and more effective therapies for persistent symptoms. PMID:18672213

Exploiting for Breast Cancer Control a Proposed Unified Mechanism for Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy

DTIC Science & Technology

2008-05-01

associated hormones or hCG to virgin female rats either before or after MNU treatment elicits persistent serum AFP levels, thereby explaining why breast...cancer appearance is inhibited when employing either treatment sequence; (2) Giving hCG to estrogenized SCID mice bearing human breast cancer...that is elicited by injection of the animals with high E3 doses. (3) In an “all-human” in vitro system, hCG elicits hAFP from cultured HepG2 human

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study

PubMed Central

2011-01-01

Background Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. Methods A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrolment. Results Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. Conclusions Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population. PMID:21251265

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study.

PubMed

Low, Andrea J; Clayton, Tim; Konate, Issouf; Nagot, Nicolas; Ouedraogo, Abdoulaye; Huet, Charlotte; Didelot-Rousseau, Marie-Noelle; Segondy, Michel; Van de Perre, Philippe; Mayaud, Philippe

2011-01-20

Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrollment. Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤ 200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population.

Radioiodine thyroid remnant ablation after recombinant human thyrotropin or thyroid hormone withdrawal in patients with high-risk differentiated thyroid cancer.

PubMed

Pitoia, Fabián; Marlowe, Robert J; Abelleira, Erika; Faure, Eduardo N; Bueno, Fernanda; Schwarzstein, Diego; Lutfi, Rubén Julio; Niepomniszcze, Hugo

2012-01-01

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Strategies used by helicobacter pylori to establish persistent infection

PubMed Central

Abadi, Amin Talebi Bezmin

2017-01-01

Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche. PMID:28522905

Wastewater Treatment Plants as Chemical Observatories to Forecast Ecological and Human Health Risks of Manmade Chemicals

PubMed Central

Venkatesan, Arjun K.; Halden, Rolf U.

2014-01-01

Thousands of chemicals have been identified as contaminants of emerging concern (CECs), but prioritizing them concerning ecological and human health risks is challenging. We explored the use of sewage treatment plants as chemical observatories to conveniently identify persistent and bioaccumulative CECs, including toxic organohalides. Nationally representative samples of sewage sludge (biosolids) were analyzed for 231 CECs, of which 123 were detected. Ten of the top 11 most abundant CECs in biosolids were found to be high-production volume chemicals, eight of which representing priority chemicals, including three flame retardants, three surfactants and two antimicrobials. A comparison of chemicals detected in nationally representative biological specimens from humans and municipal biosolids revealed 70% overlap. This observed co-occurrence of contaminants in both matrices suggests that the analysis of sewage sludge can inform human health risk assessments by providing current information on toxic exposures in human populations and associated body burdens of harmful environmental pollutants. PMID:24429544

Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology

PubMed Central

Shackman, Alexander J.; Fox, Andrew S.; Oler, Jonathan A.; Shelton, Steven E.; Oakes, Terrence R.; Davidson, Richard J.; Kalin, Ned H.

2016-01-01

Children with an anxious temperament (AT) are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression, and co-morbid substance abuse. Individuals with extreme AT often show persistent distress in the absence of immediate threat and this contextually inappropriate anxiety predicts future symptom development. Despite its clear clinical relevance, the neural circuitry governing the maladaptive persistence of anxiety remains unknown. Here, we used a well-established nonhuman primate model of childhood temperament and high-resolution 18fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to understand the neural systems governing persistent anxiety and clarify their relevance to early-life phenotypic risk. We focused on BI, a core component of anxious temperament, because it affords the moment-by-moment temporal resolution needed to assess contextually appropriate and inappropriate anxiety. From a pool of 109 peri-adolescent rhesus monkeys, we formed groups characterized by high or low levels of BI, as indexed by freezing in response to an unfamiliar human intruder’s profile. The High-BI group showed consistently elevated signs of anxiety and wariness across more than 2 years of assessments. At the time of brain imaging, 1.5 years after initial phenotyping, the High-BI group showed persistently elevated freezing during a 30-min ‘recovery’ period following an encounter with the intruder — more than an order of magnitude greater than the Low-BI group — and this was associated with increased metabolism in the bed nucleus of the stria terminalis, a key component of the central extended amygdala. These observations provide a neurobiological framework for understanding the early phenotypic risk to develop anxiety-related psychopathology, for accelerating the development of improved interventions, and for understanding the origins of childhood temperament. PMID:27573879

New clinical trial will test immunotherapy for type of HPV infection | Center for Cancer Research

Cancer.gov

Vulvar high-grade squamous intraepithelial lesion (HSIL) is caused by chronic infection with the human papillomavirus (HPV) type 16. Patients with vulvar HSIL have an increased risk of developing cancer. Lesions are usually treated surgically. However, the vulvar lesions commonly recur because of persistent systemic infection with HPV. Christian Hinrichs, M.D., a Lasker

Awareness of Diagnosis and Knowledge of HPV in Women Patients: Data from a Multi-Site Study

ERIC Educational Resources Information Center

McCree, Donna Hubbard; Daley, Ellen M.; Gorbach, Pamina; Hamm, Robert M.; Sharpe, Patricia A.; Brandt, Heather M.; McFarlane, Mary; Kerndt, Peter; McDermott, Robert J.; Perrin, Karen M.; St. Lawrence, Janet S.

2010-01-01

Background: Persistent infection with high-risk types of human papillomavirus (HPV) is associated with cervical and other anogenital cancers. Purpose: This paper reports results of awareness of an HPV diagnosis and HPV knowledge from a multi-site study of HPV knowledge, attitudes and behavior, and the impact of an HPV diagnosis on women and their…

Longitudinal Evaluation of Language Impairment in Youth With Perinatally Acquired Human Immunodeficiency Virus (HIV) and Youth With Perinatal HIV Exposure

PubMed Central

Redmond, Sean M.; Yao, Tzy-Jyun; Russell, Jonathan S.; Rice, Mabel L.; Hoffman, Howard J.; Siberry, George K.; Frederick, Toni; Purswani, Murli; Williams, Paige L.

2016-01-01

Background Language impairment (LI) risk is increased for perinatally acquired human immunodeficiency virus-infected (PHIV) and perinatally exposed to HIV but uninfected (PHEU) youth. This study evaluates the persistence of LI in these groups. Methods The Clinical Evaluation of Language Fundamentals was repeated on participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol 18 months postbaseline. Regression models identified factors associated with change in standardized score (SC) and the resolution or development of LI. Results Of 319 participants, 112 had LI at baseline. Upon re-evaluation, SCs were highly stable and changes were similar in PHIV (n = 212) and PHEU (n = 107) participants. Those with family history of language delays had a 2.39 point lower mean increase in SCs than those without, after controlling for demographic and socioeconomic factors and baseline LI status. Among PHIV participants, CD4 count <350 cells/mm3 was associated with lower mean SC change (4.32 points), and exposure to combination antiretroviral therapy (cART) or protease inhibitors (PIs) was associated with a higher mean SC change (5.93 and 4.19 points, respectively). Initial LI was persistent in most cases (78%); 20 new cases occurred (10%). Female sex was associated with higher odds of LI resolution. Among PHIV, duration and baseline cART and history of PI use were associated with LI resolution; higher percentage of detectable viral loads before baseline was associated with lower odds of resolution. Conclusions The PHIV and PHEU youth are at risk for persistent LI, and family history of language delays was a risk factor for persistence of problems. Measures of successful HIV treatment predicted more favorable outcomes among PHIV youth. PMID:27856674

Towards modelling flood protection investment as a coupled human and natural system

NASA Astrophysics Data System (ADS)

O'Connell, P. E.; O'Donnell, G.

2013-06-01

Due to a number of recent high profile flood events and the apparent threat from global warming, governments and their agencies are under pressure to make proactive investments to protect people living in floodplains. However, adopting a proactive approach as a universal strategy is not affordable. It has been argued that delaying expensive and essentially irreversible capital decisions could be a prudent strategy in situations with high future uncertainty. This paper firstly uses Monte Carlo simulation to explore the performance of proactive and reactive investment strategies using a rational cost-benefit approach in a natural system with varying levels of persistence/interannual variability in Annual Maximum Floods. It is found that, as persistence increases, there is a change in investment strategy optimality from proactive to reactive. This could have implications for investment strategies under the increasingly variable climate that is expected with global warming. As part of the emerging holistic approaches to flood risk management, there is increasing emphasis on stakeholder participation in determining where and when flood protection investments are made, and so flood risk management is becoming more people-centred. As a consequence, multiple actors are involved in the decision-making process, and the social sciences are assuming an increasingly important role in flood risk management. There is a need for modelling approaches which can couple the natural and human system elements. It is proposed that Coupled Human and Natural System (CHANS) modelling could play an important role in understanding the motivations, actions and influence of citizens and institutions and how these impact on the effective delivery of flood protection investment. A framework for using Agent Based Modelling of human activities leading to flood investments is outlined, and some of the challenges associated with implementation are discussed.

Towards modelling flood protection investment as a coupled human and natural system

NASA Astrophysics Data System (ADS)

O'Connell, P. E.; O'Donnell, G.

2014-01-01

Due to a number of recent high-profile flood events and the apparent threat from global warming, governments and their agencies are under pressure to make proactive investments to protect people living in floodplains. However, adopting a proactive approach as a universal strategy is not affordable. It has been argued that delaying expensive and essentially irreversible capital decisions could be a prudent strategy in situations with high future uncertainty. This paper firstly uses Monte Carlo simulation to explore the performance of proactive and reactive investment strategies using a rational cost-benefit approach in a natural system with varying levels of persistence/interannual variability in annual maximum floods. It is found that, as persistence increases, there is a change in investment strategy optimality from proactive to reactive. This could have implications for investment strategies under the increasingly variable climate that is expected with global warming. As part of the emerging holistic approaches to flood risk management, there is increasing emphasis on stakeholder participation in determining where and when flood protection investments are made, and so flood risk management is becoming more people-centred. As a consequence, multiple actors are involved in the decision-making process, and the social sciences are assuming an increasingly important role in flood risk management. There is a need for modelling approaches which can couple the natural and human system elements. It is proposed that coupled human and natural system (CHANS) modelling could play an important role in understanding the motivations, actions and influence of citizens and institutions and how these impact on the effective delivery of flood protection investment. A framework for using agent-based modelling of human activities leading to flood investments is outlined, and some of the challenges associated with implementation are discussed.

Risk factors for persistent gestational trophoblastic neoplasia.

PubMed

Kuyumcuoglu, Umur; Guzel, Ali Irfan; Erdemoglu, Mahmut; Celik, Yusuf

2011-01-01

This retrospective study evaluated the risk factors for persistent gestational trophoblastic disease (GTN) and determined their odds ratios. This study included 100 cases with GTN admitted to our clinic. Possible risk factors recorded were age, gravidity, parity, size of the neoplasia, and beta-human chorionic gonadotropin levels (beta-hCG) before and after the procedure. Statistical analyses consisted of the independent sample t-test and logistic regression using the statistical package SPSS ver. 15.0 for Windows (SPSS, Chicago, IL, USA). Twenty of the cases had persistent GTN, and the differences between these and the others cases were evaluated. The size of the neoplasia and histopathological type of GTN had no statistical relationship with persistence, whereas age, gravidity, and beta-hCG levels were significant risk factors for persistent GTN (p < 0.05). The odds ratios (95% confidence interval (CI)) for age, gravidity, and pre- and post-evacuation beta-hCG levels determined using logistic regression were 4.678 (0.97-22.44), 7.315 (1.16-46.16), 2.637 (1.41-4.94), and 2.339 (1.52-3.60), respectively. Patient age, gravidity, and beta-hCG levels were risk factors for persistent GTN, whereas the size of the neoplasia and histopathological type of GTN were not significant risk factors.

Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer.

PubMed

Wang, Sophia S; Bratti, M Concepcion; Rodríguez, Ana Cecilia; Herrero, Rolando; Burk, Robert D; Porras, Carolina; González, Paula; Sherman, Mark E; Wacholder, Sholom; Lan, Z Elizabeth; Schiffman, Mark; Chanock, Stephen J; Hildesheim, Allan

2009-01-01

We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (P(trend) = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (P(trend) = .009). Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

A comparison of water quality criteria for the Great Lakes based on human and wildlife health

USGS Publications Warehouse

Ludwig, James P.; Giesy, John P.; Summer, Cheryl L.; Bowerman, William; Aulerich, Richard J.; Bursian, Steven J.; Auman, Heidi J.; Jones, Paul D.; Williams, Lisa L.; Tillitt, Donald E.; Gilbertson, Michael

1993-01-01

Water quality criteria (WQC) can be derived in several ways. The usual techniques involve hazard and risk assessment procedures. For non-persistent, non-biomagnified compounds and elements, WQC are experimentally derived from their acute and chronic toxicity to aquatic organisms. For those persistent chlorinated hydrocarbons (PCHs) that are bioaccumulated and biomagnified, these traditional techniques have not been effective, partly because effects higher in the food web were not considered. Polychlorinated biphenyls (PCBs) are the bioaccumulative synthetic chemicals of primary toxicological significance to the Great Lakes biota which have caused widespread injury to wildlife. In the Laurentian Great Lakes, the primary emphasis of hazard assessments has been on the potential for adverse effects in humans who eat fish. The primary regulatory endpoint of traditional hazard and risk assessments underlying current WQC are the probabilities of additional cancers occurring in the human population. The analysis presented here indicates that this is not adequate to restore sensitive wildlife species that are highly exposed to PCBs, especially those that have suffered serious population declines. Because WQC are legal instruments, the methods of deriving WQC have large implications for remediation, litigation, and damage assessments. Here WQC are derived for six species based on the responses of wildlife in the field or produced by feeding fish to surrogate species, rather than projecting a potential of increased cancer rates in humans. If the most sensitive wildlife species are restored and protected for very sensitive reproductive endpoints, then all components of the ecosystem, including human health, should be more adequately protected. The management of Great Lakes wildlife requires an understanding of the injury and causal relationships to persistent toxic substances.

Critical Knowledge Gaps in Our Understanding of Environmental Cycling and Transmission of Leptospira spp.

PubMed Central

Olivas, Sonora

2017-01-01

ABSTRACT Exposure to soil or water contaminated with the urine of Leptospira-infected animals is the most common way in which humans contract leptospirosis. Entire populations can be at high risk of leptospirosis while working in inundated fields, when engaging in aquatic sports, or after periods of heavy rainfall. The risk of infection after contact with these environmental sources depends on the ability of Leptospira bacteria to survive, persist, and infect new hosts. Multiple variables such as soil and water pH, temperature, and even environmental microbial communities are likely to shape the environmental conditions needed by the pathogen to persist. Here we review what is known about the environmental phase of the infectious Leptospira transmission cycle and identify knowledge gaps that will serve as a guide for future research. PMID:28754706

Unusual coexistence of opportunistic lung infections in a human immunodeficiency virus positive patient suffering from persistent Pneumocystis jirovecii pneumonia: a case report.

PubMed

Ponces Bento, D; Esteves, F; Matos, O; Miranda, A C; Ventura, F; Araújo, C; Mansinho, K

2013-01-01

It is well established that HIV patients are at high risk of opportunistic infections (OI), like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP). We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA), cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy that were crucial for patient recovery. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Transmission of high-risk human papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland.

PubMed

Rintala, Marjut A M; Grénman, Seija E; Puranen, Mirja H; Isolauri, Erika; Ekblad, Ulla; Kero, Pentti O; Syrjänen, Stina M

2005-01-01

The Finnish HPV Family Study is a prospective cohort study assessing the dynamics of human papillomavirus (HPV) transmission between parents and infant. Serial genital and oral scrapings from 76 families, including mother, father, and infant, and semen samples were collected over 2 years of follow-up, analyzed by nested PCR, and confirmed by hybridization with 12 high-risk (HR) HPV types. The most common HPV profile was HR HPV in all family members (29%), followed by HPV-positive mother-infant pairs (26%). HPV-positive father-infant pairs were less frequent (11%), and in six (8%) families, only the infant was HR HPV positive. The prevalence of genital HR HPV in the parents ranged from 13 to 25%, and that of oral HPV ranged from 8 to 34%. In the infants, HPV DNA was detected in 15% of the genital and 10% of the oral samples at birth, reaching peaks of 18 and 21%, respectively, at 6 months, and declining to 10% at 24 months. Persistent HPV in the mother was a risk factor for oral HPV in the infant (odds ratio [OR], 5.69; 95% confidence interval [95% CI], 1.5 to 21.3), while oral HPV in the mother at 6 months was a risk factor for genital HR HPV (OR, 6.38; 95% CI, 1.15 to 35.32). No such independent risk could be attributed to subclinical HPV in the father. Persistent maternal cervical HPV and subclinical oral HPV affect the risk of infant HPV. The age of 6 months is a critical point for the infant to acquire or be free of HR HPV DNA.

Effect of adolescent substance use and antisocial behavior on the development of early adulthood depression.

PubMed

Choi, Tai Kiu; Worley, Matthew J; Trim, Ryan S; Howard, David; Brown, Sandra A; Hopfer, Christian J; Hewitt, John K; Wall, Tamara L

2016-04-30

Major depressive disorder (MDD) is a prevalent and frequently comorbid psychiatric disorder. This study evaluates the development of depressive symptoms, MDD diagnosis, and suicidal ideation in a high-risk sample (N=524) diagnosed with conduct disorder (CD) and substance use disorder (SUD) symptoms as youth and re-assessed approximately 6.5 years later. Dual trajectory classes of both alcohol and other drug use (AOD) and antisocial behavior (ASB), previously identified using latent class growth analyses (LCGA), were used to predict depression outcomes. The Dual Chronic, Increasing AOD/Persistent ASB, and Decreasing Drugs/Persistent ASB classes had higher past-week depression scores, more past-year MDD symptoms, and were more likely to have past-year MDD than the Resolved class. The Dual Chronic and Decreasing Drugs/Persistent ASB classes also had more past-year MDD symptoms than the Persistent AOD/Adolescent ASB class. Youth at highest risk for developing or maintaining depression in adulthood had the common characteristic of persistent antisocial behavior. This suggests young adulthood depression is associated more with persistent antisocial behavior than with persistent substance use in comorbid youth. As such, interventions targeting high-risk youth, particularly those with persistent antisocial behavior, are needed to help reduce the risk of severe psychosocial consequences (including risk for suicide) in adulthood. Published by Elsevier Ireland Ltd.

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

The Intracellular Life of Cryptococcus neoformans

PubMed Central

Coelho, Carolina; Bocca, Anamelia L.; Casadevall, Arturo

2016-01-01

Cryptococcus neoformans is a fungal pathogen with worldwide distribution. Serological studies of human populations show a high prevalence of human infection, which rarely progresses to disease in immunocompetent hosts. However, decreased host immunity places individuals at high risk for cryptococcal disease. The disease can result from acute infection or reactivation of latent infection, in which yeasts within granulomas and host macrophages emerge to cause disease. In this review, we summarize what is known about the cellular recognition, ingestion, and killing of C. neoformans and discuss the unique and remarkable features of its intracellular life, including the proposed mechanisms for fungal persistence and killing in phagocytic cells. PMID:24050625

High turnover drives prolonged persistence of influenza in managed pig herds

PubMed Central

Aguas, Ricardo; Riley, Steven; Loeffen, Willie L. A.; Wood, James L. N.; Grenfell, Bryan T.

2016-01-01

Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the ‘critical herd size’ (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV. PMID:27358277

Progression and regression of cervical pap test lesions in an urban AIDS clinic in the combined antiretroviral therapy era: a longitudinal, retrospective study.

PubMed

Lofgren, Sarah M; Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

2015-05-01

Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval.

Progression and Regression of Cervical Pap Test Lesions in an Urban AIDS Clinic in the Combined Antiretroviral Therapy Era: A Longitudinal, Retrospective Study

PubMed Central

Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

2015-01-01

Abstract Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval. PMID:25693769

Where Does Human Plague Still Persist in Latin America?

PubMed Central

Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Galan, Deise I.; Bertherat, Eric; Ruiz, Alfonso; Dumit, Elsy; Gabastou, Jean Marc; Espinal, Marcos A.

2014-01-01

Background Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. Aims The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Methods Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Results Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899–2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Discussion Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested. PMID:24516682

Where does human plague still persist in Latin America?

PubMed

Schneider, Maria Cristina; Najera, Patricia; Aldighieri, Sylvain; Galan, Deise I; Bertherat, Eric; Ruiz, Alfonso; Dumit, Elsy; Gabastou, Jean Marc; Espinal, Marcos A

2014-02-01

Plague is an epidemic-prone disease with a potential impact on public health, international trade, and tourism. It may emerge and re-emerge after decades of epidemiological silence. Today, in Latin America, human cases and foci are present in Bolivia, Brazil, Ecuador, and Peru. The objective of this study is to identify where cases of human plague still persist in Latin America and map areas that may be at risk for emergence or re-emergence. This analysis will provide evidence-based information for countries to prioritize areas for intervention. Evidence of the presence of plague was demonstrated using existing official information from WHO, PAHO, and Ministries of Health. A geo-referenced database was created to map the historical presence of plague by country between the first registered case in 1899 and 2012. Areas where plague still persists were mapped at the second level of the political/administrative divisions (counties). Selected demographic, socioeconomic, and environmental variables were described. Plague was found to be present for one or more years in 14 out of 25 countries in Latin America (1899-2012). Foci persisted in six countries, two of which have no report of current cases. There is evidence that human cases of plague still persist in 18 counties. Demographic and poverty patterns were observed in 11/18 counties. Four types of biomes are most commonly found. 12/18 have an average altitude higher than 1,300 meters above sea level. Even though human plague cases are very localized, the risk is present, and unexpected outbreaks could occur. Countries need to make the final push to eliminate plague as a public health problem for the Americas. A further disaggregated risk evaluation is recommended, including identification of foci and possible interactions among areas where plague could emerge or re-emerge. A closer geographical approach and environmental characterization are suggested.

Algae-mediated removal of selected pharmaceutical and personal care products (PPCPs) from Lake Mead water.

PubMed

Bai, Xuelian; Acharya, Kumud

2017-03-01

The persistence and fate of pharmaceutical and personal care products (PPCPs) in the Lake Mead ecosystem are particularly important considering the potential ecological risks and human health impacts. This study evaluated the removal of five common PPCPs (i.e., trimethoprim, sulfamethoxazole, carbamazepine, ciprofloxacin, and triclosan) from Lake Mead water mediated by the green alga Nannochloris sp. The results from the incubation studies showed that trimethoprim and carbamazepine were highly resistant to uptake in the algal cultural medium and were measured at approximately 90%-100% of the applied dose after 14days of incubation. Sulfamethoxazole was found relatively persistent, with >60% of the applied dose remaining in the water after 14days, and its removal was mainly caused by algae-mediated photolysis. However, ciprofloxacin and triclosan dissipated significantly and nearly 100% of the compounds were removed from the water after 7days of incubation under 24h of light. Ciprofloxacin and triclosan were highly susceptible to light, and their estimated half-lives were 12.7hours for ciprofloxacin and 31.2hours for triclosan. Algae-mediated sorption contributed to 11% of the removal of trimethoprim and sulfamethoxazole, 13% of the removal of carbamazepine, and 27% of the removal of triclosan from the lake water. This research showed that 1) trimethoprim, sulfamethoxazole, and carbamazepine are quite persistent in aquatic environments and may potentially affect human health via drinking water intake; 2) photolysis is the dominant pathway to remove ciprofloxacin from aquatic ecosystems, which indicates that ciprofloxacin may have lower ecological risks compared with other PPCPs; and 3) triclosan can undergo photolysis as well as algae-mediated uptake and it may potentially affect the food web because of its high toxicity to aquatic species. Copyright © 2017 Elsevier B.V. All rights reserved.

Nonvenereal Transmission of Human T-Cell Lymphotropic Viruses in Zambia

DTIC Science & Technology

1991-06-01

mortality from postnecrotic cirrhosis and hepatocellular carcinoma in Mansa, both of which are frequently encountered at the Mansa hospital. The age...postnecrotic cirrhosis and hepatocellular carcinoma and whether hepatitis C virus (HEV) was prevalent in the community. It was not clear whether the high...least one study suggests that most anti-HCV-positive patients with persistent hepatitis are at risk for the development of hepatocellular carcinoma (11

Neuroimmune Basis of Alcoholic Brain Damage

PubMed Central

Crews, Fulton T.; Vetreno, Ryan P.

2017-01-01

Alcohol-induced brain damage likely contributes to the dysfunctional poor decisions associated with alcohol dependence. Human alcoholics have a global loss of brain volume that is most severe in the frontal cortex. Neuroimmune gene induction by binge drinking increases neurodegeneration through increased oxidative stress, particularly NADPH oxidase-induced oxidative stress. In addition, HMGB1-TLR4 and innate immune NF-κB target genes are increased leading to persistent and sensitized neuroimmune responses to ethanol and other agents that release HMGB1 or directly stimulate TLR receptors and/or NMDA receptors. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of adolescent alcohol abuse lead to significant frontal cortical degeneration and show the most severe loss of hippocampal neurogenesis. Adolescence is a period of high risk for ethanol-induced neurodegeneration and alterations in brain structure, gene expression, and maturation of adult phenotypes. Together, these findings support the hypothesis that adolescence is a period of risk for persistent and long-lasting increases in brain neuroimmune gene expression that promote persistent and long-term increases in alcohol consumption, neuroimmune gene induction, and neurodegeneration that we find associated with alcohol use disorders. PMID:25175868

Parenteral Transmission of the Novel Human Parvovirus PARV4

PubMed Central

Manning, Ashleigh; Kenneil, Rachel; Carnie, Frances W.; Bell, Jeanne E.

2007-01-01

Transmission routes of PARV4, a newly discovered human parvovirus, were investigated by determining frequencies of persistent infections using autopsy samples from different risk groups. Predominantly parenteral routes of transmission were demonstrated by infection restricted to injection drug users and persons with hemophilia and absence of infection in homosexual men with AIDS and low-risk controls. PMID:18252117

HUMAN HEALTH RISK EVALUATION OF WEATHERED TOXAPHENE

EPA Science Inventory

Coastal/estuarine sediments are repositories for persistent organic pollutants (POPs). Sediment-associated POPs such as the chlorinated pesticide toxaphene accumulate in aquatic wildlife with the potential for transferred to higher organisms (fish, marine mammals, birds, humans) ...

Living with avian FLU--Persistence of the H5N1 highly pathogenic avian influenza virus in Egypt.

PubMed

Njabo, Kevin Yana; Zanontian, Linda; Sheta, Basma N; Samy, Ahmed; Galal, Shereen; Schoenberg, Frederic Paik; Smith, Thomas B

2016-05-01

H5N1 highly pathogenic avian influenza virus (HPAIV) continues to cause mortality in poultry and threaten human health at a panzootic scale in Egypt since it was reported in 2006. While the early focus has been in Asia, recent evidence suggests that Egypt is an emerging epicenter for the disease. Despite control measures, epizootic transmission of the disease continues. Here, we investigate the persistence of HPAIV across wild passerine birds and domestic poultry between 2009 and 2012 and the potential risk for continuous viral transmission in Egypt. We use a new weighted cross J-function to investigate the degree and spatial temporal nature of the clustering between sightings of infected birds of different types, and the risk of infection associated with direct contact with infected birds. While we found no infection in wild birds, outbreaks occurred year round between 2009 and 2012, with a positive interaction between chickens and ducks. The disease was more present in the years 2010 and 2011 coinciding with the political unrest in the country. Egypt thus continues to experience endemic outbreaks of avian influenza HPAIV in poultry and an increased potential risk of infection to other species including humans. With the current trends, the elimination of the HPAIV infection is highly unlikely without a complete revamp of current policies. The application of spatial statistics techniques to these types of data may help us to understand the characteristics of the disease and may subsequently allow practitioners to explore possible preventive solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

PubMed Central

Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

The presence of anti-Tat antibodies is predictive of long-term nonprogression to AIDS or severe immunodeficiency: findings in a cohort of HIV-1 seroconverters.

PubMed

Rezza, Giovanni; Fiorelli, Valeria; Dorrucci, Maria; Ciccozzi, Massimo; Tripiciano, Antonella; Scoglio, Arianna; Collacchi, Barbara; Ruiz-Alvarez, Maria; Giannetto, Concettina; Caputo, Antonella; Tomasoni, Lina; Castelli, Francesco; Sciandra, Mauro; Sinicco, Alessandro; Ensoli, Fabrizio; Buttò, Stefano; Ensoli, Barbara

2005-04-15

The human immunodeficiency virus (HIV) type 1 Tat protein plays a key role in the life cycle of the virus and in pathogenesis and is highly conserved among HIV subtypes. On the basis of this and of safety, immunogenicity, and efficacy findings in monkeys, Tat is being tested as a vaccine in phase 1 trials. Here, we evaluated the incidence and risk of progression to advanced HIV disease by anti-Tat serostatus in a cohort of 252 HIV-1 seroconverters. The risk of progression was lower in the anti-Tat-positive subjects than in the anti-Tat-negative subjects. Progression was faster in the persistently anti-Tat-negative subjects than in the transiently anti-Tat-positive subjects, and no progression was observed in the persistently anti-Tat-positive subjects.

Future human health research directions for the Canadian Northern Contaminants Program.

PubMed

Donaldson, Shawn G; Curren, Meredith S; Adlard, Bryan; Provost, Jonathan; Leech, Tara; Tikhonov, Constantine; Feeley, Mark; Tomlinson, Scott; Shearer, Russel

2013-01-01

Studies conducted in the mid-1980s and early 1990s demonstrated that persistent organic pollutants (POPs) and metals were reaching the Arctic ecosystem at unexpectedly high levels, many of which had no Arctic or Canadian sources. Epidemiological and toxicological studies in Canada and in other countries have found that these contaminants may pose a risk to human health. The objective of this paper is to provide the foundation for the discussion on future northern human health research under the Northern Contaminants Program (NCP) in Canada. This short discussion of human health priorities will help guide a path forward for future northern human health research in Canada to address on-going and new health concerns related to contaminants exposure in the Canadian Arctic.

Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women.

PubMed

Ngamkham, Jarunya; Boonmark, Krittika; Phansri, Thainsang

2016-01-01

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/ bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human β-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

Glatiramer acetate treatment persistence - but not adherence - in multiple sclerosis patients is predicted by health-related quality of life and self-efficacy: a prospective web-based patient-centred study (CAIR study).

PubMed

Jongen, Peter Joseph; Lemmens, Wim A; Hoogervorst, Erwin L; Donders, Rogier

2017-03-14

In patients with relapsing remitting multiple sclerosis (RRMS) the persistence of and adherence to disease modifying drug (DMD) treatment is inadequate. To take individualised measures there is a need to identify patients with a high risk of non-persistence or non-adherence. As patient-related factors have a major influence on persistence and adherence, we investigated whether health-related quality of life (HRQoL) and self-efficacy could predict persistence or adherence. In a prospective web-based patient-centred study in 203 RRMS patients, starting treatment with glatiramer acatete (GA) 20 mg subcutaneously daily, we measured physical and mental HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire), functional and control self-efficacy (Multiple Sclerosis Self-Efficacy Scale), the 12-month persistence rate and, in persistent patients, the percentage of missed doses. HRQoL and self-efficacy were compared between persistent and non-persistent patients, and between adherent and non-adherent patients. Logistic regression analysis was used to assess whether persistence and adherence were explained by HRQoL and self-efficacy. Persistent patients had higher baseline physical (mean 58.1 [standard deviation, SD] 16.9) and mental HRQoL (63.8 [16.8]) than non-persistent patients (49.5 [17.6]; 55.9 [20.4]) (P = 0.001; P = 0.003) with no differences between adherent and non-adherent patients (P = 0.46; P = 0.54). Likewise, in persistent patients function (752 [156]) and control self-efficacy (568 [178]) were higher than in non-persistent patients (689 [173]; 491 [192]) (P = 0.009; P = 0.004), but not in adherent vs. non-adherent patients (P = 0.26; P = 0.82). Logistic regression modelling identified physical HRQoL and control self-efficacy as factors that explained persistence. Based on predicted scores from the model, patients were classified into quartiles and the percentage of non-persistent patients per quartile was calculated: non-persistence in the highest quartile was 23.4 vs. 53.2% in the lowest quartile. Risk differentiation with respect to adherence was not possible. Based on these findings we propose a practical work-up scheme to identify patients with a high risk of non-persistence and to identify persistence-related factors. Findings suggest that pre-treatment physical HRQoL and control self-efficacy may identify RRMS patients with a high risk of early discontinuation of injectable DMD treatment. Targeting of high-risk patients may enable the efficient use of persistence-promoting measures. Nederlands Trial Register code: NTR2432 .

Laser capture microdissection as a tool to evaluate human papillomavirus genotyping and methylation as biomarkers of persistence and progression of anal lesions

PubMed Central

Cornall, Alyssa M; Roberts, Jennifer M; Molano, Monica; Machalek, Dorothy A; Phillips, Samuel; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Garland, Suzanne M; Tabrizi, Sepehr N

2015-01-01

Introduction Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. Methods and analysis HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. Ethics and dissemination The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to participants and the community through study newsletters, and through peer-reviewed publications and international conferences. PMID:26310402

Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study.

PubMed

Machalek, Dorothy A; Wark, John D; Tabrizi, Sepehr N; Hopper, John L; Bui, Minh; Dite, Gillian S; Cornall, Alyssa M; Pitts, Marian; Gertig, Dorota; Erbas, Bircan; Garland, Suzanne M

2017-02-01

Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.

Persistent oral human papillomavirus infection is associated with smoking and elevated salivary immunoglobulin G concentration.

PubMed

Haukioja, Anna; Asunta, Maribel; Söderling, Eva; Syrjänen, Stina

2014-09-01

Prevalence and risk factors for human papillomavirus (HPV) persistence in oral mucosa are largely unknown. Furthermore, the antiviral effects of saliva in the outcome of oral HPV infections are unexplored. To compare the levels of selected salivary defence proteins in women with a persistent oral HPV infection and in those without any signs of oral HPV. Lifestyle factors including the use of oral contraceptives, oral sex, smoking and alcohol drinking habits were also assessed. This nested case-control study of the Finnish Family HPV Study included 60 women with a persistent oral HPV infection and 117 women who remained HPV DNA negative throughout a 6-year follow-up. Whole saliva samples and oral scrapings for HPV testing were collected at the same visit. The oral HPV status was related to salivary concentrations of lactoferrin, lysozyme, IgA, IgG, total protein and sodium as well as to the use of oral contraceptives, oral sex, smoking and alcohol drinking habits. Women with a persistent oral HPV infection had higher salivary levels of IgG (p=0.007) and lysozyme (p=0.002, when adjusted to the total protein concentration), than those without an HPV infection. Lactoferrin and IgA concentrations were not related to the HPV-status. Smoking increased the risk of a persistent oral HPV infection (p=0.020), but the oral HPV status was not related to other life-style factors studied. Smoking is a risk factor for a persistent oral HPV infection. Oral HPV infection may be associated with increased concentrations of salivary IgG and lysozyme. Copyright © 2014 Elsevier B.V. All rights reserved.

Persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in conventional or enriched cages

USDA-ARS?s Scientific Manuscript database

: Because Salmonella Enteritidis can be deposited inside eggs laid by infected hens, the prevalence of this pathogen in commercial egg-producing flocks is an important risk factor for human illness. Opportunities for the introduction, transmission, and persistence of salmonellae in poultry are poten...

Persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in conventional or enriched cages.

USDA-ARS?s Scientific Manuscript database

Because Salmonella Enteritidis can be deposited inside eggs laid by infected hens, the prevalence of this pathogen in commercial egg-producing flocks is an important risk factor for human illness. Opportunities for the introduction, transmission, and persistence of salmonellae in poultry are potenti...

Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA.

PubMed

Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M; Germar, Maria Julieta V; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C; Skinner, S Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Peters, Klaus; Tjalma, Wiebren A A; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

2014-08-15

We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Risk of Newly Detected Infections and Cervical Abnormalities in Women Seropositive for Naturally Acquired Human Papillomavirus Type 16/18 Antibodies: Analysis of the Control Arm of PATRICIA

PubMed Central

Castellsagué, Xavier; Naud, Paulo; Chow, Song-Nan; Wheeler, Cosette M.; Germar, Maria Julieta V.; Lehtinen, Matti; Paavonen, Jorma; Jaisamrarn, Unnop; Garland, Suzanne M.; Salmerón, Jorge; Apter, Dan; Kitchener, Henry; Teixeira, Julio C.; Skinner, S. Rachel; Limson, Genara; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y.; Schwarz, Tino F.; Poppe, Willy A. J.; Bosch, F. Xavier; de Carvalho, Newton S.; Peters, Klaus; Tjalma, Wiebren A. A.; Safaeian, Mahboobeh; Raillard, Alice; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence

2014-01-01

Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15–25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242–794), 204 (95% CI, 129–480), and 480 (95% CI, 250–5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type. PMID:24610876

Estimating and mapping the population at risk of sleeping sickness.

PubMed

Simarro, Pere P; Cecchi, Giuliano; Franco, José R; Paone, Massimo; Diarra, Abdoulaye; Ruiz-Postigo, José Antonio; Fèvre, Eric M; Mattioli, Raffaele C; Jannin, Jean G

2012-01-01

Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from "very high" to "very low," and to estimate the corresponding at-risk population. Approximately 70 million people distributed over a surface of 1.55 million km(2) are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported. Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.

Long-term persistence of oral human papillomavirus type 16: the HPV Infection in Men (HIM) study.

PubMed

Pierce Campbell, Christine M; Kreimer, Aimée R; Lin, Hui-Yi; Fulp, William; O'Keefe, Michael T; Ingles, Donna J; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2015-03-01

Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18 to 64 years [median, 36 years; interquartile range (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months [median infection duration, 7.3 months; 95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. ©2015 American Association for Cancer Research.

Longitudinal Evaluation of Language Impairment in Youth With Perinatally Acquired Human Immunodeficiency Virus (HIV) and Youth With Perinatal HIV Exposure.

PubMed

Redmond, Sean M; Yao, Tzy-Jyun; Russell, Jonathan S; Rice, Mabel L; Hoffman, Howard J; Siberry, George K; Frederick, Toni; Purswani, Murli; Williams, Paige L

2016-12-01

Language impairment (LI) risk is increased for perinatally acquired human immunodeficiency virus-infected (PHIV) and perinatally exposed to HIV but uninfected (PHEU) youth. This study evaluates the persistence of LI in these groups. The Clinical Evaluation of Language Fundamentals was repeated on participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol 18 months postbaseline. Regression models identified factors associated with change in standardized score (SC) and the resolution or development of LI. Of 319 participants, 112 had LI at baseline. Upon re-evaluation, SCs were highly stable and changes were similar in PHIV (n = 212) and PHEU (n = 107) participants. Those with family history of language delays had a 2.39 point lower mean increase in SCs than those without, after controlling for demographic and socioeconomic factors and baseline LI status. Among PHIV participants, CD4 count <350 cells/mm 3 was associated with lower mean SC change (4.32 points), and exposure to combination antiretroviral therapy (cART) or protease inhibitors (PIs) was associated with a higher mean SC change (5.93 and 4.19 points, respectively). Initial LI was persistent in most cases (78%); 20 new cases occurred (10%). Female sex was associated with higher odds of LI resolution. Among PHIV, duration and baseline cART and history of PI use were associated with LI resolution; higher percentage of detectable viral loads before baseline was associated with lower odds of resolution. The PHIV and PHEU youth are at risk for persistent LI, and family history of language delays was a risk factor for persistence of problems. Measures of successful HIV treatment predicted more favorable outcomes among PHIV youth. © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Human Hallucinogen Research: Guidelines for Safety

PubMed Central

Johnson, Matthew W.; Richards, William A.; Griffiths, Roland R.

2010-01-01

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (“bad trip”), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment, and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. PMID:18593734

Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.

PubMed

Hu, Ting; Yang, Pei; Zhu, Hongmei; Chen, Xinlian; Xie, Xiaoyan; Yang, Mei; Liu, Shanling; Wang, He

2015-04-02

Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown. In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution. A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05). The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

Retrospective study of the influence of HPV persistence on outcomes among women with high-risk HPV infections and negative cytology.

PubMed

Bogani, Giorgio; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Martinelli, Fabio; Signorelli, Mauro; Leone Roberti Maggiore, Umberto; Chiappa, Valentina; Scaffa, Cono; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

2017-07-01

To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia. The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed. There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses. Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. © 2017 International Federation of Gynecology and Obstetrics.

Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal.

PubMed

Vallejo Casas, Juan A; Mena Bares, Luisa M; Gálvez Moreno, Maria A; Moreno Ortega, Estefanía; Marlowe, Robert J; Maza Muret, Francisco R; Albalá González, María D

2016-06-01

Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.

Future human health research directions for the Canadian Northern Contaminants Program

PubMed Central

Donaldson, Shawn G.; Curren, Meredith S.; Adlard, Bryan; Provost, Jonathan; Leech, Tara; Tikhonov, Constantine; Feeley, Mark; Tomlinson, Scott; Shearer, Russel

2013-01-01

Studies conducted in the mid-1980s and early 1990s demonstrated that persistent organic pollutants (POPs) and metals were reaching the Arctic ecosystem at unexpectedly high levels, many of which had no Arctic or Canadian sources. Epidemiological and toxicological studies in Canada and in other countries have found that these contaminants may pose a risk to human health. The objective of this paper is to provide the foundation for the discussion on future northern human health research under the Northern Contaminants Program (NCP) in Canada. This short discussion of human health priorities will help guide a path forward for future northern human health research in Canada to address on-going and new health concerns related to contaminants exposure in the Canadian Arctic. PMID:24282784

Frequency and persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in enriched colony cages at different stocking densities

USDA-ARS?s Scientific Manuscript database

Human infections with Salmonella Enteritidis are often attributed to the consumption of contaminated eggs, so the prevalence of this pathogen in egg-laying poultry is an important public health risk factor. Numerous and complex environmental influences on Salmonella persistence and transmission are ...

Statistical Survey of Persistent Organic Pollutants: Risk Estimations to Humans and Wildlife through Consumption of Fish from U.S. Rivers

EPA Science Inventory

U.S. EPA conducted a national statistical survey of fish tissue contamination at 540 river sites (representing 82 954 river km) in 2008–2009, and analyzed samples for 50 persistent organic pollutants (POPs), including 21 PCB congeners, 8 PBDE congeners, and 21 organoc...

Frequency and persistence of fecal shedding of Salmonella Enteritidis by experimentally infected laying hens housed in enriched colony cages at different stocking densities

USDA-ARS?s Scientific Manuscript database

Human Salmonella Enteritidis infections are often linked with consuming contaminated eggs, so the prevalence of this pathogen in egg-laying poultry is an important risk factor for public health. Salmonella persistence and transmission in commercial egg producing flocks are influenced by the complex ...

Effects of defined mixtures of persistent organic pollutants (POPs) on multiple cellular responses in the human hepatocarcinoma cell line, HepG2, using high content analysis screening

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Jodie; Berntsen, Hanne Friis; Zimmer, Karin Elisabeth

Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential. Most studies focus on single compound effects, however as humans are exposed to several POPs simultaneously, investigating exposure effects of real life POP mixtures on human health is necessary. A defined mixture of POPs was used, where the compound concentration reflected its contribution to the levels seen in Scandinavian human serum (total mix). Several sub mixtures representing different classes of POPs were also constructed. The perfluorinated (PFC) mixture contained six perfluorinated compounds, brominated (Br) mixture contained seven brominated compounds,more » chlorinated (Cl) mixture contained polychlorinated biphenyls and also p,p’-dichlorodiphenyldichloroethylene, hexachlorobenzene, three chlordanes, three hexachlorocyclohexanes and dieldrin. Human hepatocarcinoma (HepG2) cells were used for 2 h and 48 h exposures to the seven mixtures and analysis on a CellInsight™ NXT High Content Screening platform. Multiple cytotoxic endpoints were investigated: cell number, nuclear intensity and area, mitochondrial mass and membrane potential (MMP) and reactive oxygen species (ROS). Both the Br and Cl mixtures induced ROS production but did not lead to apoptosis. The PFC mixture induced ROS production and likely induced cell apoptosis accompanied by the dissipation of MMP. Synergistic effects were evident for ROS induction when cells were exposed to the PFC + Br mixture in comparison to the effects of the individual mixtures. No significant effects were detected in the Br + Cl, PFC + Cl or total mixtures, which contain the same concentrations of chlorinated compounds as the Cl mixture plus additional compounds; highlighting the need for further exploration of POP mixtures in risk assessment. - Highlights: • High content analysis (HCA) is a novel approach for determining toxicity of complex mixtures. • Multiple cytotoxic endpoints were investigated for defined mixtures of persistent organic pollutants (POPs). • POP mixtures are based on levels relevant to human exposure. • POP mixtures can increase ROS induction and impact mitochondrial health, which could result in apoptosis. • HCA can detect pre-lethal and reversible signs of cellular stress.« less

ASBESTOS AND RELATED DURABLE FIBERS: TOO UBIQUITOUS, TOO PERSISTENT, TOO COMPLEX TO PUT HUMAN HEALTH RISKS TO REST?

EPA Science Inventory

Asbestos was used for centuries before its health risks became publicly known. Health concerns for non-occupational exposures rose at EPA's inception and these concerns quickly expanded to include risks from inhalation and ingestion of durable mineral jand synthetic fibers that w...

Artificial intelligence estimates the impact of human papillomavirus types in influencing the risk of cervical dysplasia recurrence: progress toward a more personalized approach.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Leone Roberti Maggiore, Umberto; Taverna, Francesca; Lombardo, Claudia; Borghi, Chiara; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-22

The objective of this study was to determine whether the pretreatment human papillomavirus (HPV) genotype might predict the risk of cervical dysplasia persistence/recurrence. Retrospective analysis of prospectively collected data of consecutive 5104 women who underwent the HPV-DNA test were matched with retrospective data of women undergoing either follow-up or medical/surgical treatment(s) for genital HPV-related infection(s). Artificial neuronal network (ANN) analysis was used in order to weight the importance of different HPV genotypes in predicting cervical dysplasia persistence/recurrence. ANN simulates a biological neuronal system from both the structural and functional points of view: like neurons, ANN acquires knowledge through a learning-phase process and allows weighting the importance of covariates, thus establishing how much a variable influences a multifactor phenomenon. Overall, 5104 women were tested for HPV. Among them, 1273 (25%) patients underwent treatment for HPV-related disorders. LASER conization and cervical vaporization were performed in 807 (59%) and 386 (30%) patients, respectively, and secondary cervical conization in 45 (5.5%). ANN technology showed that the most important genotypes predicting cervical dysplasia persistence/recurrence were HPV-16 (normalized importance: 100%), HPV-59 (normalized importance: 51.2%), HPV-52 (normalized importance: 47.7%), HPV-18 (normalized importance: 32.8%) and HPV-45 (normalized importance: 30.2%). The pretreatment diagnosis of all of those genotypes, except HPV-45, correlated with an increased risk of cervical dysplasia persistence/recurrence; the pretreatment diagnosis was also arrived at using standard univariate and multivariable models (P<0.01). Pretreatment positivity for HPV-16, HPV-18, HPV-52 and HPV-59 might correlate with an increased risk of cervical dysplasia persistence/recurrence after treatment. These data might be helpful during patients' counseling and to implement new vaccination programs.

Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis.

PubMed

Kochi, Masako; Kohagura, Kentaro; Shiohira, Yoshiki; Iseki, Kunitoshi; Ohya, Yusuke

2016-01-01

The relationship between chronic inflammation and the incidence of chronic kidney disease (CKD) remained not-clear in patients with rheumatoid arthritis (RA). This study aims to examine the relationship between persistently high C-reactive protein (CRP), a marker of inflammation, and the incidence of CKD in RA. We retrospectively examined the relationship between the levels of CRP and incidence of CKD in 345 RA patients. The outcome of interest was incidence of CKD, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or positive dipstick testing for proteinuria for ≥3 months. We defined high CRP, as >3.0 mg/L. On the basis of three measurements of CRP for 6-months period, patients were divided into three groups: group 1, including patients with no high CRP values; group 2, patients with transient high CRP values (once or twice) and group 3, patients with persistently high CRP values. During a median follow-up period of 89 months, 14% of all patients developed CKD. The cumulative incidence of CKD was 7% in group 1, 14% in group 2 and 22% in group 3 (P = 0.008, log-rank test). In a multivariate analysis, including classical risk factors for CKD, persistently high CRP was an independent predictor of the incidence of CKD (hazard ratio, 3.00; 95% confidence interval, 1.23-8.53; P = 0.01). Persistently high CRP was a significant risk factor for the incidence of CKD. Results suggest that persistent inflammation is a marker for the high risk of CKD in RA.

The pathobiology and mechanisms of infection of HPV.

PubMed

Wood, N H; Khammissa, R A G; Chikte, U M E; Meyerov, R; Lemmer, J; Feller, L

2010-04-01

There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.

Longitudinal risk factors for persistent fatigue in adolescents.

PubMed

Viner, Russell M; Clark, Charlotte; Taylor, Stephanie J C; Bhui, Kam; Klineberg, Emily; Head, Jenny; Booy, Robert; Stansfeld, Stephen A

2008-05-01

To examine whether sedentary behavior, obesity, smoking, and depression are risk factors for persistent fatigue in adolescents. Longitudinal population-based survey. Twenty-eight randomly selected schools in east London, England, in 2001 and 2003. A total of 1880 adolescents (49% male; 81% nonwhite British) aged 11 to 12 years and 13 to 14 years in 2000. Confidential questionnaires completed in class. Persistent fatigue (extreme tiredness twice weekly or more often in the previous month at both surveys), sedentary behavior, physical activity, depressive symptoms, body mass index, and smoking. Severe fatigue was reported in 11% of participants aged 11 to 14 years and 17% of participants aged 13 to 16 years. Eighty-four participants (4%) reported persistent fatigue. Across both surveys, only 3 pupils reported chronic fatigue syndrome. In multivariate logistic regression, risk of persistent fatigue was independently associated with being sedentary for more than 4 hours per day (odds ratio = 1.6; 95% confidence interval, 1.1-2.3; P = .01), being physically active (odds ratio = 1.5; 95% confidence interval, 1.1-2.3; P = .004), and depressive symptoms (odds ratio = 2.0; 95% confidence interval, 1.5-2.7; P < .001) in the first survey, after adjustment for age, sex, and socioeconomic status. Obesity and smoking were not associated with fatigue. Persistent fatigue is common. Being highly sedentary or highly active independently increased the risk of persistent fatigue, suggesting that divergence in either direction from healthy levels of activity increases the risk for persistent fatigue. Mental health is important in the etiology of persistent fatigue. To help define effective preventive strategies, further work is needed on the mechanisms by which these factors contribute to fatigue.

COMMUNICATING RISKS OF PERSISTANT BIOACCUMULATING TOXICS IN FOODS

EPA Science Inventory

The primary route of exposure to many persistant bioaccumulating toxins (PBT) such as methyl mercury, PCDs or Dioxins is though foods. Many people, but particularly subsistence fishermen, pregnant women and children, are at high risk for methyl mercury toxicity because of their c...

Metapopulation modelling of riparian tree species persistence in river networks under climate change.

PubMed

Van Looy, Kris; Piffady, Jérémy

2017-11-01

Floodplain landscapes are highly fragmented by river regulation resulting in habitat degradation and flood regime perturbation, posing risks to population persistence. Climate change is expected to pose supplementary risks in this context of fragmented landscapes, and especially for river systems adaptation management programs are developed. The association of habitat quality and quantity with the landscape dynamics and resilience to human-induced disturbances is still poorly understood in the context of species survival and colonization processes, but essential to prioritize conservation and restoration actions. We present a modelling approach that elucidates network connectivity and landscape dynamics in spatial and temporal context to identify vital corridors and conservation priorities in the Loire river and its tributaries. Alteration of flooding and flow regimes is believed to be critical to population dynamics in river ecosystems. Still, little is known of critical levels of alteration both spatially and temporally. We applied metapopulation modelling approaches for a dispersal-limited tree species, white elm; and a recruitment-limited tree species, black poplar. In different model steps the connectivity and natural dynamics of the river landscape are confronted with physical alterations (dams/dykes) to species survival and then future scenarios for climatic changes and potential adaptation measures are entered in the model and translated in population persistence over the river basin. For the two tree species we highlighted crucial network zones in relation to habitat quality and connectivity. Where the human impact model already shows currently restricted metapopulation development, climate change is projected to aggravate this persistence perspective substantially. For both species a significant drawback to the basin population is observed, with 1/3 for elm and ¼ for poplar after 25 years already. But proposed adaptation measures prove effective to even bring metapopulation strength and persistence up to a level above the current level. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

PubMed Central

Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

2012-01-01

Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

HUMAN HEALTH IMPACTS OF EXPOSURE TO POPS

EPA Science Inventory

The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative and undergo long range transport. These POPs include 9 pesticides, polychlorinated d...

Paying the pipers: Mitigating the impact of anticoagulant rodenticides on predators and scavengers

USGS Publications Warehouse

Elliott, John E.; Rattner, Barnett A.; Shore, Richard F.; van den Brink, Nico W.

2016-01-01

Anticoagulant rodenticides, mainly second-generation forms, or SGARs, dominate the global market for rodent control. Introduced in the 1970s to counter genetic resistance in rodent populations to first-generation compounds such as warfarin, SGARs are extremely toxic and highly effective killers. However, their tendency to persist and accumulate in the body has led to the widespread contamination of terrestrial predators and scavengers. Commercial chemicals that are classified by regulators as persistent, bio-accumulative, and toxic (PBT) chemicals and that are widely used with potential environmental release, such as dichloro-diphenyl-trichloroethane (DDT) or polychlorinated biphenyls (PCBs), have been removed from commerce. However, despite consistently failing ecological risk assessments, SGARs remain in use because of the demand for effective rodent-control options and the lack of safe and humane alternatives. Although new risk-mitigation measures for rodenticides are now in effect in some countries, the contamination and poisoning of nontarget wildlife are expected to continue. Here, we suggest options to further attenuate this problem.

The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature.

PubMed

Taylor, Sylvia; Bunge, Eveline; Bakker, Marina; Castellsagué, Xavier

2016-06-14

Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy. Not applicable, as systematic review of the literature.

Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Nonsynonymous Variant at SLC39A8 in Europeans.

PubMed

Li, Ming; Wu, Dong-Dong; Yao, Yong-Gang; Huo, Yong-Xia; Liu, Jie-Wei; Su, Bing; Chasman, Daniel I; Chu, Audrey Y; Huang, Tao; Qi, Lu; Zheng, Yan; Luo, Xiong-Jian

2016-01-01

Natural selection has played important roles in optimizing complex human adaptations. However, schizophrenia poses an evolutionary paradox during human evolution, as the illness has strongly negative effects on fitness, but persists with a prevalence of ~0.5% across global populations. Recent studies have identified numerous risk variations in diverse populations, which might be able to explain the stable and high rate of schizophrenia morbidity in different cultures and regions, but the questions about why the risk alleles derived and maintained in human gene pool still remain unsolved. Here, we studied the evolutionary pattern of a schizophrenia risk variant rs13107325 (P < 5.0 × 10(-8) in Europeans) in the SLC39A8 gene. We found the SNP is monomorphic in Asians and Africans with risk (derived) T-allele totally absent, and further evolutionary analyses showed the T-allele has experienced recent positive selection in Europeans. Subsequent exploratory analyses implicated that the colder environment in Europe was the likely selective pressures, ie, when modern humans migrated "out of Africa" and moved to Europe mainland (a colder and cooler continent than Africa), new alleles derived due to positive selection and protected humans from risk of hypertension and also helped them adapt to the cold environment. The hypothesis was supported by our pleiotropic analyses with hypertension and energy intake as well as obesity in Europeans. Our data thus provides an intriguing example to illustrate a possible mechanism for maintaining schizophrenia risk alleles in the human gene pool, and further supported that schizophrenia is likely a product caused by pleiotropic effect during human evolution. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2015-01-01

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

Persistent Organic Pollutants as Risk Factors for Obesity and Diabetes.

PubMed

Yang, Chunxue; Kong, Alice Pik Shan; Cai, Zongwei; Chung, Arthur C K

2017-11-02

The rising prevalence of obesity and diabetes cannot be fully explained by known risk factors, such as unhealthy diet, a sedentary lifestyle, and family history. This review summarizes the available studies linking persistent organic pollutants (POPs) to obesity and diabetes and discusses plausible underlying mechanisms. Increasing evidence suggest that POPs may act as obesogens and diabetogens to promote the development of obesity and diabetes and induce metabolic dysfunction. POPs are synthesized chemicals and are used widely in our daily life. These chemicals are resistant to degradation in chemical or biological processes, which enable them to exist in the environment persistently and to be bio-accumulated in animal and human tissue through the food chain. Increasingly, epidemiologic studies suggest a positive association between POPs and risk of developing diabetes. Understanding the relationship of POPs with obesity and diabetes may shed light on preventive strategies for obesity and diabetes.

Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer.

PubMed

Kennedy, E M; Powell, D R; Li, Z; Bell, J S K; Barwick, B G; Feng, H; McCrary, M R; Dwivedi, B; Kowalski, J; Dynan, W S; Conneely, K N; Vertino, P M

2018-04-30

Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56 Fe and 28 Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56 Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges ("shores") of CpG islands. The 28 Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56 Fe ion sensitive sites, but not those affected by X ray or 28 Si ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.

Persistent and High-Level Expression of Human Liver Prolidase in Vivo in Mice Using Adenovirus

DTIC Science & Technology

2013-01-01

types of nerve agents and pesticide compounds, is mostly exported into the circulation [11]. Similarly, human paraoxonase1, a promising enzyme in the...of human butyrylcholinesetrase results in persistent high-level transgene expression in vivo, Chem. Biol. Interact. 175 (2008) 327– 331. [11] K...paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxon, Gene Ther. 18 (2011) 250–257. [14

Insecticide Treated Camouflage Sceening Reduces Sand Fly Numbers in Leishmania-Endemic Regions in Kenya

USDA-ARS?s Scientific Manuscript database

Current U.S. military operations in deserts face persistent threats from sand flies that transmit human Leishmania. In this study we investigated the efficacy of artificial barriers treated with residual insecticide to potentially reduce the risk of human infection from leishmaniasis by reducing the...

PERSISTENT CONTAMINANTS: NEW PRIORITIES, NEW CONCERNS

EPA Science Inventory

The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative, and undergo long range transport. These POPs include 9 pesticides, polychlorin...

Intermittent versus Persistent Wolff-Parkinson-White Syndrome in Children: Electrophysiologic Properties and Clinical Outcomes.

PubMed

Kiger, Michelle E; McCanta, Anthony C; Tong, Suhong; Schaffer, Michael; Runciman, Martin; Collins, Kathryn K

2016-01-01

Intermittent Wolff-Parkinson-White (WPW) syndrome is considered to have a lower risk of sudden death. Fewer data exist regarding electrophysiologic (EP) characteristics and the natural history of intermittent WPW in children. All patients with WPW age 1-18 years at a single institution (1996-2013) were reviewed. Patients with intermittent preexcitation were compared to those with loss of preexcitation on Holter/exercise testing and those with persistent preexcitation. High-risk accessory pathway (AP) was defined as AP effective refractory period (APERP), block cycle length, or shortest preexcited RR interval during atrial fibrillation ≤250 ms. A total of 295 patients were included: 226 (76.6%) persistent, 39 (13.2%) intermittent, and 30 (10.2%) loss of preexcitation Holter/exercise. There were no differences in symptoms between groups. Median interquartile range APERP was significantly longer in intermittent WPW (380 [320, 488] ms vs 320 [300, 350] ms persistent, 310 [290, 330] ms loss of preexcitation Holter/exercise; P = 0.0008). At baseline, there was no difference between groups in frequency of high-risk pathways. However, when isoproterenol values were included, high-risk pathways were more frequent among patients with loss of preexcitation on Holter/exercise (54% vs 16% persistent, 11% intermittent; P = 0.005). There was one death in a patient with loss of preexcitation on exercise testing, no EP study, and prior drug use. A second patient with persistent WPW and APERP 270 ms required resuscitation following a methadone overdose. Intermittent preexcitation in children does not connote a lower risk AP by EP criteria or reduced symptoms. The low number of pediatric WPW patients who develop preexcited atrial fibrillation or sudden death warrants larger studies to investigate these outcomes. ©2015 Wiley Periodicals, Inc.

Parsing apart the persisters: Etiological mechanisms and criminal offense patterns of moderate- and high-level persistent offenders.

PubMed

Amemiya, Jamie; Vanderhei, Susan; Monahan, Kathryn C

2017-08-01

Longitudinal investigations that have applied Moffitt's dual taxonomic framework to criminal offending have provided support for the existence of adolescent-limited and life-course persistent antisocial individuals, but have also identified additional trajectories. For instance, rather than a single persistent trajectory, studies have found both high-level and moderate-level persistent offenders. To inform theory and progress our understanding of chronic antisocial behavior, the present study used a sample of serious adolescent offenders (N =1,088) followed from middle adolescence to early adulthood (14-25 years), and examined how moderate-level persistent offenders differed from low-rate, desisting, and high-level persistent offenders. Results indicated that moderate-level persisters' etiology and criminal offense patterns were most similar to high-level persisters, but there were notable differences. Specifically, increasing levels of contextual adversity characterized both moderate-level and high-level persisting trajectories, but moderate-level persisters reported consistently lower levels of environmental risk. While both high- and moderate-level persisters committed more drug-related offenses in early adulthood compared to adolescence, moderate-level persisters engaged in lower levels of antisocial behavior across all types of criminal offenses. Taken cumulatively, the findings of this study suggest that sociocontextual interventions may be powerful in reducing both moderate- and high-level persistence in crime.

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se; Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se; Bottai, Matteo, E-mail: Matteo.Bottai@ki.se

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNAmore » damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.« less

Is colposcopy necessary at twelve months after large loop excision of the transformation zone? A clinical audit.

PubMed

Thompson, Valerie; Marin, Raymond

2013-12-01

The purpose of this study was to review outcomes from LLETZ (large loop excision of the transformation zone) procedures carried out for high-grade cervical intraepithelial neoplasia (CIN), in particular findings at colposcopy, cytology and HR-HPV(high-risk human papilloma virus) result to assess whether colposcopy provides any additional information in the management of women at 12 months. We retrospectively analysed 252 patients who had a LLETZ procedure for a HSIL (high-grade squamous intraepithelial lesion) between January 2005 and December 2010. Eighty per cent of women who had a LLETZ procedure for HSIL were reviewed in our colposcopy clinic at 12 months after the procedure. Colposcopy at 12 months after LLETZ was documented as unsatisfactory for 30% of these women. The sensitivity of colposcopy at 12 months after LLETZ was 0.47, and the specificity was 0.95. Colposcopy examination is an insensitive tool for detection of persisting HPV-related change after excision of high-grade CIN. Its usefulness to investigate persistent or recurrent HSIL is further reduced by the high rate of unsatisfactory colposcopy examinations after a LLETZ procedure. Papanicolaou smear and HRHPV tests may be adequate follow-up at 12 months after LLETZ for women at low risk of recurrence of HSIL. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

PubMed

DeVries, Zachary C; Santangelo, Richard G; Barbarin, Alexis M; Schal, Coby

2018-01-01

Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust). Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment.

Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes

PubMed Central

Santangelo, Richard G.; Barbarin, Alexis M.; Schal, Coby

2018-01-01

Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust). Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment. PMID:29432483

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies

PubMed Central

Wang, Li; Guyatt, Gordon H.; Kennedy, Sean A.; Romerosa, Beatriz; Kwon, Henry Y.; Kaushal, Alka; Chang, Yaping; Craigie, Samantha; de Almeida, Carlos P.B.; Couban, Rachel J.; Parascandalo, Shawn R.; Izhar, Zain; Reid, Susan; Khan, James S.; McGillion, Michael; Busse, Jason W.

2016-01-01

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case–control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24–1.48), radiotherapy (OR 1.35, 95% CI 1.16–1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73–3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03–1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01–1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery. PMID:27402075

Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs) in Taiwan

PubMed Central

Tsai, Wen-Tien

2010-01-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years. PMID:21139852

Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan.

PubMed

Tsai, Wen-Tien

2010-10-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years.

Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response

PubMed Central

Grant, Sarah Schmidt; Hung, Deborah T.

2013-01-01

Certain bacterial pathogens are able to evade the host immune system and persist within the human host. The consequences of persistent bacterial infections potentially include increased morbidity and mortality from the infection itself as well as an increased risk of dissemination of disease. Eradication of persistent infections is difficult, often requiring prolonged or repeated courses of antibiotics. During persistent infections, a population or subpopulation of bacteria exists that is refractory to traditional antibiotics, possibly in a non-replicating or metabolically altered state. This review highlights the clinical significance of persistent infections and discusses different in vitro models used to investigate the altered physiology of bacteria during persistent infections. We specifically focus on recent work establishing increased protection against oxidative stress as a key element of the altered physiologic state across different in vitro models and pathogens. PMID:23563389

The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease.

PubMed

Stewart, James B; Chinnery, Patrick F

2015-09-01

Common genetic variants of mitochondrial DNA (mtDNA) increase the risk of developing several of the major health issues facing the western world, including neurodegenerative diseases. In this Review, we consider how these mtDNA variants arose and how they spread from their origin on one single molecule in a single cell to be present at high levels throughout a specific organ and, ultimately, to contribute to the population risk of common age-related disorders. mtDNA persists in all aerobic eukaryotes, despite a high substitution rate, clonal propagation and little evidence of recombination. Recent studies have found that de novo mtDNA mutations are suppressed in the female germ line; despite this, mtDNA heteroplasmy is remarkably common. The demonstration of a mammalian mtDNA genetic bottleneck explains how new germline variants can increase to high levels within a generation, and the ultimate fixation of less-severe mutations that escape germline selection explains how they can contribute to the risk of late-onset disorders.

Phenomenological Analysis of the Experiences of Underprepared College Students Who Persist

ERIC Educational Resources Information Center

Larsen, Mary Jo

2016-01-01

This study examined the experiences of six college participants who entered college with many risk-factors for drop-out, but who persisted to graduation. The present research was conducted at a private, liberal arts university. All participants possessed multiple risk factors for drop-out including low high school academic performance,…

Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

PubMed

Hillemanns, Peter; Einstein, Mark H; Iversen, Ole Erik

2015-02-01

Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

The factor structure of static actuarial items: its relation to prediction.

PubMed

Barbaree, Howard E; Langton, Calvin M; Peacock, Edward J

2006-04-01

Principal components analysis was conducted on items contained in actuarial instruments used with adult sex offenders, including: the Rapid Assessment of Sex Offender Risk for Recidivism (RASORR), the Static-99, the Violence Risk Appraisal Guide (VRAG), the Sex Offender Risk Appraisal Guide (SORAG), and the Minnesota Sex Offender Screening Tool-Revised (MnSOST-R). In a data set that included child molesters and rapists (N = 311), six interpretable components were identified: Antisocial Behavior, Child Sexual Abuse, Persistence, Detached Predatory Behavior, Young and Single, and Male Victim(s). The RRASOR was highly correlated with Persistence, and the VRAG and SORAG were highly correlated with Antisocial Behavior. Antisocial Behavior was a significant predictor of violent recidivism, while Persistence and Child Sexual Abuse were significant predictors of sexual recidivism.

Risk Reduction from Minimization of Persistent, Bioaccumulative, and Toxic Waste Materials Within the U.S. Industrial Solid Waste Management System

EPA Science Inventory

This study addressed three questions of interest in national-scale solid and hazardous waste management decision-making within the United States: 1) can we quantify the reduction in risk to human and ecological receptors resulting from the reduction of certain industrial waste s...

A Risk Algorithm for the Persistence of Suicidal Thoughts and Behaviors During College.

PubMed

Mortier, Philippe; Kiekens, Glenn; Auerbach, Randy P; Cuijpers, Pim; Demyttenaere, Koen; Green, Jennifer G; Kessler, Ronald C; Nock, Matthew K; Zaslavsky, Alan M; Bruffaerts, Ronny

2017-07-01

The primary aims of this study are to (a) identify patterns of suicidal thoughts and behaviors (STB) during college among students with lifetime pre-matriculation STB and (b) develop a risk-screening algorithm for persistence of pre-matriculation STB during college. Data come from the Leuven College Surveys, a series of prospective cohort studies of all incoming KU Leuven University freshmen. In the academic year 2012-2013, 4,889 incoming freshmen (73.2% response rate) provided baseline data on sociodemographic variables, childhood-adolescent traumatic experiences, 12-month stressful experiences, 12-month mental disorders, 12-month STB, and severity markers of pre-matriculation STB. A total of 2,566 students (69.3% conditional response rate) participated in 12- and 24-month follow-up surveys during the first 2 college years. Thirteen percent (weighted n = 535) of incoming freshmen reported lifetime pre-matriculation STB. Of those, 28.0% reported 12-month STB in 1 follow-up assessment, and another 27.7%, in both follow-up assessments. High persistence of STB (ie, 12-month STB in 2 follow-up assessments) was most strongly associated with severity markers of pre-matriculation STB, with odds ratios in the 2.4-10.3 range and population attributable risk proportions between 9.2% and 50.8%. When the aim was for less than 50% of false-positive cases (positive predictive value = 54.4%), a multivariate predictive risk algorithm (cross-validated area under the curve = 0.79) situated 59.9% of highly persistent cases among the 30% respondents with highest baseline predicted risk. An individualized web-based screening approach is a promising strategy to identify students at the time of university entrance who may be at high risk for STB persistence during their academic career. © Copyright 2017 Physicians Postgraduate Press, Inc.

A RISK ALGORITHM FOR THE PERSISTENCE OF SUICIDAL THOUGHTS AND BEHAVIORS DURING COLLEGE

PubMed Central

Mortier, Philippe; Kiekens, Glenn; Auerbach, Randy P.; Cuijpers, Pim; Demyttenaere, Koen; Green, Jennifer G.; Kessler, Ronald C.; Nock, Matthew K.; Zaslavsky, Alan M.; Bruffaerts, Ronny

2017-01-01

OBJECTIVE The primary aims are to: (a) identify patterns of suicidal thoughts and behaviors (STB) during college among students with lifetime pre-matriculation STB and (b) develop a risk-screening algorithm for persistence of pre-matriculation STB during college. METHODS Data come from the Leuven College Surveys, a series of prospective cohort studies of all incoming KU Leuven University freshmen. In the academic year 2012 and 2013, 4,889 incoming freshmen (73.2% response rate) provided baseline data on socio-demographic variables, childhood-adolescent traumatic experiences, 12-month stressful experiences, 12-month mental disorders, 12-month STB, and severity markers of pre-matriculation STB. A total of 2,566 students (69.3% conditional response rate) participated in 12- and 24-month follow-up surveys during the first two college years. RESULTS Thirteen percent (weighted n=535) of incoming freshmen reported lifetime pre-matriculation STB. Of those, 28.0% reported 12-month STB in one follow-up assessment and another 27.7% in both follow-up assessments. High persistence of STB (i.e., 12-month STB in two follow-up assessments) was most strongly associated with severity markers of pre-matriculation STB, with odds ratios in the 2.4–10.3 range and population attributable risk proportions between 9.2% and 50.8%. When aiming for less than 50% of false positive cases (PPV=54.4%), a multivariate predictive risk algorithm (cross-validated AUC=0.79) situated 59.9% of highly persistent cases among the 30% respondents with highest baseline predicted risk. CONCLUSION An individualized web-based screening approach is a promising strategy to identify students at the onset of university who may be at high risk for STB persistence during their academic career. PMID:28640991

Work factors as predictors of persistent fatigue: a prospective study of nurses' aides.

PubMed

Eriksen, W

2006-06-01

To identify work factors that predict persistent fatigue in nurses' aides. The sample comprised 5547 Norwegian nurses' aides, not on leave when they completed a mailed questionnaire in 1999. Of these, 4645 (83.7%) completed a second questionnaire 15 months later. The outcome measure was the occurrence of persistent fatigue, defined as having felt "usually fatigued" or "always fatigued" in daytime during the previous 14 days. In respondents without persistent fatigue at baseline, medium and high work demands, heavy smoking, being single, and having long term health problems were associated with increased risk of persistent fatigue at follow up. Medium and high rewards for well done work, medium levels of leadership fairness, and regular physical exercise were associated with reduced risk of persistent fatigue at follow up. In respondents with persistent fatigue at baseline, medium and high levels of positive challenges at work, high support from immediate superior, medium feedback about quality of one's work, and changes of work or work tasks that resulted in less heavy work or lower work pace were associated with increased odds of recovery (no persistent fatigue at follow up). Working in a nursing home and being intensely bothered by long term health problems were associated with reduced odds of recovery. High demands and lack of rewards at work may cause persistent fatigue in nurses' aides. Reduction of demands, adequate feedback, and mental stimulation in the form of support and positive challenges may facilitate recovery in those who have persistent fatigue. Leaders in the health services may be in a position to regulate factors that influence the level of fatigue in nurses' aides.

Timing of Biochemical Failure and Distant Metastasis for Low, Intermediate, and High Risk Prostate Cancer after Radiotherapy

PubMed Central

Morgan, Peter B.; Hanlon, Alexandra L.; Horwitz, Eric M.; Buyyounouski, Mark K.; Uzzo, Robert G.; Pollack, Alan

2007-01-01

Condensed Abstract The timing of biochemical failure and distant metastasis after radiotherapy for low, intermediate and high-risk prostate cancer was determined. The patterns of failure suggest that the majority of early failures were due to subclinical micrometastases present at diagnosis, whereas a late wave of metastasis at 10–12 years in every risk group was consistent with tumor spread from local persistence of disease. Background The relationship of prostate cancer risk group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. We sought to differentiate early failures due to subclinical micrometastasis at presentation from late failures due to local persistence. Methods A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. The interval hazard rates of DM and BF, using ASTRO and Phoenix (Nadir+2) definitions, were determined for men with low, intermediate, and high risk disease. Results Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P<.0001) and Nadir+2 BF (P<.0001). The preponderance (87%) of ASTRO BF occurred ≤4 years after RT, while Nadir+2 BF was more evenly spread over years 1–12, with 43% at >4 years. The hazard of Nadir+2 BF persisted in years 8–12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early and late peaks) for intermediate and high risk patients, but no distinct early wave was evident for low risk patients. Conclusions ASTRO BF underestimates late BF due to backdating. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low risk tumors supports the hypothesis that occult micrometastases contributed to the early wave. PMID:17520705

Genomic characterization of recurrent mold infections in thoracic transplant recipients.

PubMed

Messina, Julia A; Wolfe, Cameron R; Hemmersbach-Miller, Marion; Milano, Carmelo; Todd, Jamie L; Reynolds, John; Alexander, Barbara D; Schell, Wiley A; Cuomo, Christina A; Perfect, John R

2018-05-31

Invasive mold disease in thoracic organ transplant recipients is a well-recognized complication, but the long-term persistence of molds within the human body and evasion of host defenses has not been well-described. We present 2 cases of invasive mold disease (Verruconis gallopava and Aspergillus fumigatus) in thoracic transplant recipients who had the same mold cultured years prior to the invasive disease presentation. The paired isolates from the index and recurrent infections in both patients were compared using whole-genome sequencing to determine if the same strain of mold caused both the index and recurrent infections. In Case 1, the isolates were found to be of the same strain indicating that the initial colonizing isolate identified pre-transplant eventually caused invasive mold disease post-transplant while in Case 2, the 2 isolates were not of the same strain. These results demonstrate the distinct possibility of molds both persisting within the human body for years prior to invasive mold disease or the long-term risk of recurrent, persistent infection with more than one strain. Further studies of long-term molecular epidemiology of IMD and risk factors for mold persistence in transplant recipients are encouraged. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of Surgery and Radiation Therapy in the Management of Gestational Trophoblastic Disease

PubMed Central

Hanna, Rabbie K.

2010-01-01

The primary management of hydatidiform moles remains surgical evacuation followed by human chorionic gonadotropin level monitoring. Although suction dilatation and evacuation is the most frequent technique for molar evacuation, hysterectomy is a viable option in older patients who do not wish to preserve fertility. Despite advances in chemotherapy regimens for treating malignant gestational trophoblastic neoplasia, hysterectomy and other extirpative procedures continue to play a role in the management of patients with both low-risk and high-risk gestational trophoblastic neoplasia. Primary hysterectomy can reduce the amount of chemotherapy required to treat low-risk disease, whereas surgical resections, including hysterectomy, pulmonary resections, and other extirpative procedures, can be invaluable for treating highly selected patients with persistent, drug-resistant disease. Radiation therapy is also often incorporated into the multimodality therapy of patients with high-risk metastatic disease. This review discusses the indications for and the role of surgical interventions during the management of women with hydatidiform moles and malignant gestational trophoblastic neoplasia and reviews the use of radiation therapy in the treatment of women with malignant gestational trophoblastic neoplasia. PMID:20495216

Stigma and Human Rights Abuses against People Who Inject Drugs in Russia--A Qualitative Investigation to Inform Policy and Public Health Strategies.

PubMed

Lunze, Karsten; Lunze, Fatima I; Raj, Anita; Samet, Jeffrey H

2015-01-01

Drug policing practices in the Russian Federation (Russia) are often punitive and have been shown to be associated with HIV risk behaviors among people who inject drugs (PWID). Less is known about strategies to address the problem in that setting, where substance use stigma is highly persistent. A better understanding of forms, causes and consequences of drug policing in Russia could inform drug policy in a context of substantial policy resistance. This qualitative study's goal is to characterize the phenomenon of police involvement with Russian PWID and to explore strategies for drug policing in the Russian country context. Using a semi-structured interview guide, we collected data from a purposive sample of 23 key informants including PWID, police officers, and experts from civil society and international organizations in Russia. We used a thematic analysis approach to inductively generate new insight into the phenomenon of police involvement and potential strategies to address it. Policing practices involving PWID include unjustified arrests, planting of false evidence and extrajudicial syringe confiscations, and often constitute human rights violations. Russian PWID personally experienced police violence as ubiquitous, taking on various forms such as beating, unjustified arrests, verbal harassment, and coercion. The persistent societal stigma dehumanizes PWID, and such stigmatization facilitates police abuse. To address stigma and overcome the PWID-police adversity, study participants suggested fostering a mutual understanding between the police and public health sectors. Participants describe substantial human rights violations as part of policing illicit drug use in Russia. Police should include principles of effective prevention of substance use and HIV risk reduction in their trainings. Alignment of public safety and public health goals could address drug use-related risks and HIV prevention among key populations in Russia.

Persistent Expression Changes of Fibrosis Related Genes in the Lung Tissues of Rats Exposed to Lunar Dust Particles

NASA Technical Reports Server (NTRS)

Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Theriot, Corey; Zalesak, Selina; Yeshitla, Samrawit; Williams, Kyle; Wu, Honglu; James, John T.

2014-01-01

The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.

Reducing Sand Fly Numbers in Leishmania Endemic Regions in Kenya with Insecticide Treated Camouflage Screening

USDA-ARS?s Scientific Manuscript database

Current US military operations in deserts face persistent threats from sand flies that transmit human Leishmania. Methods to reduce the risk of human infection from leishmaniasis by reducing the number of sand fly vectors were investigated in Kenya. Bifenthrin treated and un-treated camouflage netti...

The persistence of Mycobacterium avium in a drinking water system, what is the risk to human health?

EPA Science Inventory

Drinking water is believed to be a major source of human exposure to nontuberculous mycobacteria (NTM) such as Mycobacterium avium. We monitored the prevalence of M. avium in a drinking water system during the addition of filtration treatment. Our goal was to determine if the pre...

Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions.

PubMed

Oppelt, Peter; Renner, Stefan P; Strick, Reiner; Valletta, Daniela; Mehlhorn, Grit; Fasching, Peter A; Beckmann, Matthias W; Strissel, Pamela L

2010-04-01

To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis, are associated with endometriosis lesions. Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction-based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. University hospital. Seventy individual patients with and without endometriosis. Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

PubMed Central

2011-01-01

Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D) on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years) primarily used vial/syringe (87%) and insulin analogs (60%). Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR < 0.80, p < 0.01). Additional predictors of non-persistence at 12 months included elderly age, increased insulin copayment, mental health comorbidity, and polypharmacy (p < 0.05 for all). Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs. PMID:21226935

House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old

PubMed Central

Llanora, Genevieve V.; Ming, Low Jia; Wei, Lee Ming

2012-01-01

Background Identifying toddlers at increased risk of developing persistent wheeze provides an opportunity for risk-reducing interventions. House dust mite (HDM) allergen sensitization might identify this group of high-risk children. Objective We examined whether a positive skin prick test (SPT) to at least 1 of the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze at age 8 to 14 years old. Methods A cohort of 78 children, who had wheezing episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were enrolled. SPT results were obtained from the National University Hospital database. Four to 9 years later, the children, currently between 8 to 14 years old, were re-assessed for persistence of asthma symptoms and other atopic disorders via a telephone interview. A validated questionnaire on current wheezing and asthma, developed by the International Study of Asthma and Allergies in Childhood, was used. Fisher's exact test was used to evaluate the association between persistence of asthma and a positive SPT. Results Of the 78 children who participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative children had persistence of asthma symptoms. There is a significant association between a positive SPT during the preschool years, and persistence of asthma (p = 0.0314 [<0.05]). Conclusion HDM sensitization at ages 2 to 5 years old in wheezing children predicts persistence of asthma after 4 to 9 years. This in turn may have benefits for management of asthma in this high-risk group. PMID:22872820

Justice heals: the impact of impunity and the fight against it on the recovery of severe human rights violations' survivors.

PubMed

Rauchfuss, Knut; Schmolze, Bianca

2008-01-01

Case studies show that traumatized refugees, who are survivors of serious human rights violations, suffer from persisting impunity in their home countries. Ongoing impunity--the inability to overcome the legal protection of the perpetrators assured by impunity laws, incomplete truthfinding, missing integral reparation and a lack of the necessary acknowledgement by society--represents an important obstacle for the recovery of survivors of serious human rights violations. There are reports describing that a high percentage of survivors shows an elevated mental vulnerability caused by impunity. Mental health problems resulting from traumatic experiences can persist or be reactivated by certain events. In particular, family members of the forcibly disappeared suffer from an incomplete mourning due to the uncertain fate of their beloved ones. The ongoing search for the forcibly disappeared under an atmosphere of impunity puts family members under high risk of retraumatization. Studies from other continents also prove that impunity severely affects mental health. Due to the global character of impunity there can be only little evidence about a positive impact of justice on mental health. Nevertheless, a few examples, in particular from Latin America, show that the combined implementation of memory, truth and justice can have a healing impact on those who suffer from trauma. They demonstrate that the fight against impunity is not only a legitimate moral struggle for human rights, but also a basic need for the sustainable recovery of survivors.

RISK COMMUNICATION TOOLS FOR FISH CONSUMPTION ADVISORIES

EPA Science Inventory

In EPA's Mercury Report to Congress an important finding ws that certain populations of subsistence fishermen are at high risk for methyl mercury toxicity because of their high consumption of contaminated fish. Often health risks of Persistent Bioaccumulative Toxicants (PBT) such...

NATIONAL WWTP EFFLUENT STUDY

EPA Science Inventory

Reports of potential wildlife risk from exposure to environmental estrogens emphasize the need to better understand both estrogenic presence and persistence in treated wastewater effluents. In addition to wildlife exposure, human exposure should also be examined, especially in si...

2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

PubMed Central

Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

2013-01-01

The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

The potential association of CMV-specific CD8+ T lymphocyte reconstitution with the risk of CMV reactivation and persistency in post allogeneic stem cell transplant patients.

PubMed

Shams El-Din, Ahmed Ali; El-Desoukey, Nermeen Ahmed; Amin Tawadrous, Dalia Gamil; Fouad, Neveen Mohammed Baha El-Din; Abdel-Mooti, Mohammed; Hotar, Said Fathy

2018-01-09

development of cytomegalovirus (CMV)-specific CD8+ T cell response is crucial in preventing symptomatic CMV infection specially, in stem cell transplant (SCT) patients. The aim of this study was to evaluate CMV-specific CD8+ T cell reconstitution in allogeneic SCT recipients and to study the possible association between CMV-specific CD8+ T cell recovery with protection from CMV reactivation and persistency. Human leuKocyte antigen (HLA)-tetramers were used for CMV-specific CD8+ cell quantitation by Flow cytometry in twenty post-allogeneic SCT patients. Nine patients (45%) developed rapid recovery of CMV-specific CD8+ cells, among them; 7 patients (78%) had no CMV reactivation in the first 95 days post-transplant. Five patients had developed persistent CMV viremia; all of them had not developed CMV-specific CD8+ recovery till day 95 post-transplant. Patients with persistent CMV viremia had a statistically significant lower means of CMV-specific CD8+ percent and absolute count compared to those without persistent viremia (p = .001, .015), respectively. The incidence of CMV reactivation and persistency was higher among patients with delayed CMV-specific CD8+ reconstitution in the first 95 days post-transplant. CMV-specific CD8+ cells can help in categorizing patients into risk groups: (early recovery/low risk) and (delayed recovery/increased risk), this tool may guide clinicians in the selection of patients who may profit from prophylactic antiviral therapy and frequent viral monitoring.

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.

PubMed

Steinberg, Benjamin A; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Hankey, Graeme J; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hacke, Werner; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Piccini, Jonathan P

2015-02-01

Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Neurotoxicity and risk assessment of brominated and alternative flame retardants.

PubMed

Hendriks, Hester S; Westerink, Remco H S

2015-01-01

Brominated flame retardants (BFRs) are widely used chemicals that prevent or slow the onset and spreading of fire. Unfortunately, many of these compounds pose serious threats for human health and the environment, indicating an urgent need for safe(r) and less persistent alternative flame retardants (AFRs). As previous research identified the nervous system as a sensitive target organ, the neurotoxicity of past and present flame retardants is reviewed. First, an overview of the neurotoxicity of BFRs in humans and experimental animals is provided, and some common in vitro neurotoxic mechanisms of action are discussed. The combined epidemiological and toxicological studies clearly underline the need for replacing BFRs. Many potentially suitable AFRs are already in use, despite the absence of a full profile of their environmental behavior and toxicological properties. To prioritize the suitability of some selected halogenated and non-halogenated organophosphorous flame retardants and inorganic halogen-free flame retardants, the available neurotoxic data of these AFRs are discussed. The suitability of the AFRs is rank-ordered and combined with human exposure data (serum concentrations, breast milk concentrations and house dust concentrations) and physicochemical properties (useful to predict e.g. bioavailability and persistence in the environment) for a first semi-quantitative risk assessment of the AFRs. As can be concluded from the reviewed data, several BFRs and AFRs share some neurotoxic effects and modes of action. Moreover, the available neurotoxicity data indicate that some AFRs may be suitable substitutes for BFRs. However, proper risk assessment is hampered by an overall scarcity of data, particularly regarding environmental persistence, human exposure levels, and the formation of breakdown products and possible metabolites as well as their toxicity. Until these data gaps in environmental behavioral and toxicological profiles are filled, large scale use of these chemicals should be cautioned.

Mortality, Disenrollment, and Spending Persistence in Medicaid and CHIP.

PubMed

DeLia, Derek

2017-03-01

Research on spending persistence has not focused on Medicaid and the Children's Health Insurance Program (Medicaid/CHIP), which includes a complex and growing population. The objective of the study was to describe patterns of expenditure persistence, mortality, and disenrollment among nondually eligible Medicaid/CHIP enrollees and identify factors predicting these outcomes. The study is based on New Jersey Medicaid/CHIP claims data from 2011 to 2014. Descriptive and multinomial regression methods were used to characterize persistently extreme spenders, defined as those appearing in the top 1% of statewide spending every year, according to demographics, Medicaid/CHIP eligibility, nursing facility residence, patient risk scores, and clinical diagnostic categories measured in 2011. Similar analyses were done for persistently high spenders (ie, always in the top 10% but not always top 1%) as well as decedents, disenrollees, and moderate spenders (ie, at least 1 year outside of the top 10%). Nondually eligible NJ Medicaid/CHIP enrollees in 2011. One fourth of extreme spenders in 2011 remained in that category throughout 2011-2014. Almost all (89.3%) of the persistently extreme spenders were aged, blind, or disabled. Within the aged, blind, or disabled population, the strongest predictors of persistently extreme spending were diagnoses involving developmental disability, HIV/AIDS, central nervous system conditions, psychiatric disorders, type 1 diabetes, and renal conditions. Individuals in nursing facilities and those with very high risk scores were more likely to die or have persistently high spending than to have persistently extreme spending. The study highlights unique features of spending persistence within Medicaid/CHIP and provides methodological contributions to the broader persistence literature.

Epidemiology of virus infection and human cancer.

PubMed

Chen, Chien-Jen; Hsu, Wan-Lun; Yang, Hwai-I; Lee, Mei-Hsuan; Chen, Hui-Chi; Chien, Yin-Chu; You, San-Lin

2014-01-01

The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years.

PubMed

Silver, Michelle I; Gage, Julia C; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Katki, Hormuzd A; Locke, Alexander; Kinney, Walter K; Castle, Philip E

2018-03-01

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2 + Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2 + might not be necessary after a negative cotest. Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more severe diagnoses. More research is needed to determine whether such prolonged management might be unnecessary following a negative cotest for those women with an initial CIN2 but otherwise only low-grade findings. Cancer Prev Res; 11(3); 165-70. ©2018 AACR . ©2018 American Association for Cancer Research.

Human papilloma virus infection and cervical dysplasia.

PubMed

Melinte-Popescu, Alina; Costăchescu, Gh

2012-01-01

Pap testing is considered to be the best screening tool for cervical cancer but there is currently great interest in the possible application of human papilloma virus (HPV) testing to supplement Pap screening for cervical cancer. To determine the prevalence of high-risk HPV types in the studied population and to explore the association between high-risk HPV types and cervical dysplasia. Cross-sectional study conducted at the Iasi Cuza Voda Obstetrics-Gynecology Hospital and Suceava County Hospital. 332 women who underwent colposcopy for cervical lesions between 2006 and 2011 were included in this study. The overall prevalence of HPV was 57.23%. HPV prevalence differs significantly in the three age groups up to 50 years. It was highest in patients below the age of 40 and progressively lower with advancing age. The overall prevalence of cervical dysplasia was 56.62%. The prevalence of cervical dysplasia was highest in the age groups up to 40 years. The most important determinant of HPV infection is age. Persistence of HPV appears to be associated with progression to squamous intraepithelial lesion. Dysplasia is often missed in a cervical sample either because of human error in screening and interpretation, or because of suboptimal quality of Pap smear. Incorporation of HPV testing into the present Pap screening program has the potential of making screening for cervical cancer more effective, and a necessary prelude to assessing this is by determining the prevalence of the high-risk types.

Reversal of papilloma growth in rabbits therapeutically vaccinated against E6 with naked DNA and/or vesicular stomatitis virus vectors

PubMed Central

Brandsma, Janet L.; Shlyankevich, Mark; Su, Yuhua; Zelterman, Daniel; Rose, John K.; Buonocore, Linda

2009-01-01

Persistent infection with high-risk human papillomaviruses (HPVs) is the greatest risk factor for the development of HPV-associated cancers. In this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant DNA and/or vesicular stomatitis virus (VSV) targeting the cottontail rabbit papillomavirus (CRPV) E6 protein. Immune responses were primed with either vector and boosted twice with the homologous or heterologous E6 vector. Over the course of 18 weeks, E6 vaccination reduced papilloma volumes to one third the volume in the controls, and the rabbits boosted with an heterologous vector tended to mount stronger responses. Small and medium-sized papillomas responded significantly but only slightly better than large papillomas. Finally the initial papilloma burden per rabbit, ranging from <100 mm3 to >1000 mm3, was not prognostic of antitumor efficacy. In summary both E6 vaccines elicited significant therapeutic immunity, and their sequential use tended to be advantageous. PMID:19615481

Fate and survival of Salmonella Typhimurium and Escherichia coli O157:H7 in repacked soil lysimeters after application of cattle slurry and human urine.

PubMed

Nyberg, Karin A; Ottoson, Jakob R; Vinnerås, Björn; Albihn, Ann

2014-09-01

Use of cattle slurry as a fertiliser is common practice around the world. Human urine use is not as common, but owing to its fertiliser value this might change in the future. It is essential to minimise the transfer of enteric pathogens through fertilisation, with respect to both animal and public health. Therefore the objective of this research was to study the survival and transport of Salmonella Typhimurium and Escherichia coli O157:H7 in two agricultural soils when applied to soil along with either cattle slurry or human urine over a period of 180 days. Both Salmonella and E. coli O157:H7 were more rapidly reduced when applied together with human urine than when applied with cattle slurry. However, both pathogens persisted in low amounts at 20 and 50 cm depth in both soils throughout the whole study period. No Salmonella or E. coli O157:H7 was detected in the leachate over the 180 day study. The risk of disease transmission is higher when cattle slurry is used as fertiliser compared with human urine. However, the risk of groundwater infiltration would be low as long as water velocity through the soil is moderate. Increased knowledge of pathogen persistence in soil after fertiliser application is a valuable tool for improving risk evaluations and formulating guidelines for the use of cattle and/or human wastes in cropping soils. © 2014 Society of Chemical Industry.

The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

PubMed Central

2012-01-01

Background Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). Methods Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. Results No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. Conclusions The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease. PMID:23148667

Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

PubMed

van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J

2017-10-01

Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially ( P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is limited. By sequencing a number of infections with known follow-up for up to 3 years, we gained initial insights into the genetic diversity of HPV16 and the effects of the viral genome on the persistence of infections. A SNP comparison between sequences obtained from clearing and persistent infections did not identify strongly acting DNA variations responsible for these infection outcomes. In addition, we identified an HPV16 reinfection event where sequencing of initial and follow-up samples showed different HPV16 variants. Based on conventional genotyping, this infection would incorrectly be considered a persistent HPV16 infection. In the context of vaccine efficacy and monitoring studies, such infections could potentially cause reduced reported efficacy or efficiency. Copyright © 2017 van der Weele et al.

Sequence-Dependent Persistence Length of Long DNA

NASA Astrophysics Data System (ADS)

Chuang, Hui-Min; Reifenberger, Jeffrey G.; Cao, Han; Dorfman, Kevin D.

2017-12-01

Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm ×41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.5% and 60%. Using Odijk's theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the percent GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.

Genital Tract HIV RNA Levels and Their Associations with Human Papillomavirus Infection and Risk of Cervical Pre-Cancer

PubMed Central

GHARTEY, Jeny; KOVACS, Andrea; BURK, Robert D.; MASSAD, L. Stewart; MINKOFF, Howard; XIE, Xianhong; D’SOUZA, Gypsyamber; XUE, Xiaonan; WATTS, D. Heather; LEVINE, Alexandra M.; EINSTEIN, Mark H.; COLIE, Christine; ANASTOS, Kathryn; ELTOUM, Isam-Eldin; HEROLD, Betsy C.; PALEFSKY, Joel M.; STRICKLER, Howard D.

2014-01-01

Objective Plasma HIV RNA levels have been associated with risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. Design/Methods In an HIV-seropositive women’s cohort with semi-annual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions sub-classified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incident severe HSIL were matched to 130 controls by age, CD4+ count, HAART use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. Results Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable [ORVL] 2.96; 95% CI: 0.99–8.84; Ptrend=0.03). However, this association became non-significant (Ptrend=0.51) following adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend=0.02) and persistence of oncogenic HPV (Ptrend=0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. Conclusion These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical pre-cancer in HIV-seropositive women, but leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumoriogenesis. PMID:24694931

Incidence trends of adenocarcinoma of the cervix in 13 European countries.

PubMed

Bray, Freddie; Carstensen, Bendix; Møller, Henrik; Zappa, Marco; Zakelj, Maja Primic; Lawrence, Gill; Hakama, Matti; Weiderpass, Elisabete

2005-09-01

Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages <75 in 13 European countries. Age-adjusted adenocarcinoma incidence rates increased throughout Europe, the rate of increase ranging from around 0.5% per annum in Denmark, Sweden, and Switzerland to >/=3% in Finland, Slovakia, and Slovenia. The increases first affected generations born in the early 1930s through the mid-1940s, with risk invariably higher in women born in the mid-1960s relative to those born 20 years earlier. The magnitude of this risk ratio varied considerably from around 7 in Slovenia to almost unity in France. Declines in period-specific risk were observed in United Kingdom, Denmark, and Sweden, primarily among women ages >30. Whereas increasing specificity of subtype with time may be responsible for some of the increases in several countries, the changing distribution and prevalence of persistent infection with high-risk human papillomavirus types, alongside an inability to detect cervical adenocarcinoma within screening programs, would accord with the temporal profile observed in Europe. The homogeneity of trends in adenocarcinoma and squamous cell carcinoma in birth cohort is consistent with the notion that they share a similar etiology irrespective of the differential capability of screen detection. Screening may have had at least some impact in reducing cervical adenocarcinoma incidence in several countries during the 1990s.

LES of Laminar-to-Turbulent Particle-Fluid Dynamics in Human and Nonhuman Primate Airways: Applications to Aerosolized Drug Delivery Animal Testing

NASA Astrophysics Data System (ADS)

Geisler, Taylor; Padhy, Sourav; Shaqfeh, Eric; Iaccarino, Gianluca

2016-11-01

Both the human health benefit and risk from the inhalation of aerosolized medications is often predicted by extrapolating experimental data taken using nonhuman primates to human inhalation. In this study, we employ Large Eddy Simulation to simulate particle-fluid dynamics in realistic upper airway models of both humans and rhesus monkeys. We report laminar-to-turbulent flow transitions triggered by constrictions in the upper trachea and the persistence of unsteadiness into the low Reynolds number bifurcating lower airway. Micro-particle deposition fraction and locations are shown to depend significantly on particle size. In particular, particle filtration in the nasal airways is shown to approach unity for large aerosols (8 microns) or high-rate breathing. We validate the accuracy of LES mean flow predictions using MRV imaging results. Additionally, particle deposition fractions are validated against experiments in 3 model airways.

Meat sources of infection for outbreaks of human trichinellosis.

PubMed

Rostami, Ali; Gamble, H Ray; Dupouy-Camet, Jean; Khazan, Hooshang; Bruschi, Fabrizio

2017-06-01

Trichinellosis is one of the most important foodborne zoonotic diseases, with worldwide distribution. While human risk for trichinellosis has historically been linked to pork, modern pork production systems and slaughter inspection programs have reduced or eliminated pork as a source for trichinellosis in many countries. While pork may no longer pose a significant risk for trichinellosis, many other animal species may be hosts for Trichinella species nematodes and when human consume meat from these animal species, there may be risk for acquiring trichinellosis. This review article describes the various non-pork meat sources of human trichinellosis outbreaks, where these outbreaks have occurred and some of the factors that contribute to human risk. The literature reviewed here provides evidence of the persistence of Trichinella as a human health risk for people who eat meat from feral and wild carnivores and scavengers, as well as some herbivores that have been shown to harbor Trichinella larvae. It points to the importance of education of hunters and consumers of these meats and meat products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contact variables for exposure to avian influenza H5N1 virus at the human-animal interface.

PubMed

Rabinowitz, P; Perdue, M; Mumford, E

2010-06-01

Although the highly pathogenic avian influenza H5N1 virus continues to cause infections in both avian and human populations, the specific zoonotic risk factors remain poorly understood. This review summarizes available evidence regarding types of contact associated with transmission of H5N1 virus at the human-animal interface. A systematic search of the published literature revealed five analytical studies and 15 case reports describing avian influenza transmission from animals to humans for further review. Risk factors identified in analytical studies were compared, and World Health Organization-confirmed cases, identified in case reports, were classified according to type of contact reported using a standardized algorithm. Although cases were primarily associated with direct contact with sick/unexpectedly dead birds, some cases reported only indirect contact with birds or contaminated environments or contact with apparently healthy birds. Specific types of contacts or activities leading to exposure could not be determined from data available in the publications reviewed. These results support previous reports that direct contact with sick birds is not the only means of human exposure to avian influenza H5N1 virus. To target public health measures and disease awareness messaging for reducing the risk of zoonotic infection with avian influenza H5N1 virus, the specific types of contacts and activities leading to transmission need to be further understood. The role of environmental virus persistence, shedding of virus by asymptomatic poultry and disease pathophysiology in different avian species relative to human zoonotic risk, as well as specific modes of zoonotic transmission, should be determined.

PEFLUOROOCTANOIC ACID-INDUCED IMMUNOMODULATION IN C57BL/6 FEMALE MICE

EPA Science Inventory

Perfluorooctanoic acid (PFOA), used in fluoropolymer production, is environmentally persistent, present in human and wildlife populations worldwide, and associated with myriad health effects in laboratory animals. A preliminary risk assessment by the US EPA identified immunosuppr...

Anal intraepithelial neoplasia: A review of diagnosis and management

PubMed Central

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-01-01

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations. PMID:28255426

Anal intraepithelial neoplasia: A review of diagnosis and management.

PubMed

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-02-15

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

Human Papillomavirus Testing in the Prevention of Cervical Cancer

PubMed Central

Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

2011-01-01

Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

Patients with Long-Term Oral Carriage Harbor High-Persister Mutants of Candida albicans▿

PubMed Central

LaFleur, Michael D.; Qi, Qingguo; Lewis, Kim

2010-01-01

Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections. PMID:19841146

Ecological, Social and Biological Risk Factors for Continued Trypanosoma cruzi Transmission by Triatoma dimidiata in Guatemala

PubMed Central

Bustamante, Dulce M.; De Urioste-Stone, Sandra M.; Juárez, José G.; Pennington, Pamela M.

2014-01-01

Background Chagas disease transmission by Triatoma dimidiata persists in Guatemala and elsewhere in Central America under undefined ecological, biological and social (eco-bio-social) conditions. Methodology Eco-bio-social risk factors associated with persistent domiciliary infestation were identified by a cross-sectional survey and qualitative participatory methods. Quantitative and qualitative data were generated regarding Trypanosoma cruzi reservoirs and triatomine hosts. Blood meal analysis and infection of insects, dogs and rodents were determined. Based on these data, multimodel inference was used to identify risk factors for domestic infestation with the greatest relative importance (>0.75). Principal Findings Blood meal analysis showed that 64% of 36 bugs fed on chickens, 50% on humans, 17% on dogs; 24% of 34 bugs fed on Rattus rattus and 21% on Mus musculus. Seroprevalence among 80 dogs was 37%. Eight (17%) of 46 M. musculus and three (43%) of seven R. rattus from households with infected triatomines were infected with T. cruzi Distinct Typing Unit I. Results from interviews and participatory meetings indicated that vector control personnel and some householders perceived chickens roosting and laying eggs in the house as bug infestation risk factors. House construction practices were seen as a risk factor for bug and rodent infestation, with rodents being perceived as a pest by study participants. Multimodel inference showed that house infestation risk factors of high relative importance are dog density, mouse presence, interior wall plaster condition, dirt floor, tile roofing and coffee tree presence. Conclusions/Significance Persistent house infestation is closely related to eco-bio-social factors that maintain productive T. dimidiata habitats associated with dogs, chickens and rodents. Triatomine, dog and rodent infections indicate active T. cruzi transmission. Integrated vector control methods should include actions that consider the role of peridomestic animals in transmission and community memberś level of knowledge, attitudes and practices associated with the disease and transmission process. PMID:25170955

Quantitative risk from fluoroquinolone-resistant Salmonella and Campylobacter due to treatment of dairy heifers with enrofloxacin for bovine respiratory disease.

PubMed

Hurd, H Scott; Vaughn, Michael B; Holtkamp, Derald; Dickson, James; Warnick, Lorin

2010-11-01

The objective of this study was to evaluate the human health impact of using fluoroquinolones to treat bovine respiratory disease (BRD) in dairy heifers less than 20 months of age. Specifically, this study quantified the probability of persistent symptoms in humans treated with a fluoroquinolone, for a fluoroquinolone-resistant Campylobacter, Salmonella, or multidrug-resistant (MDR) Salmonella infection acquired following the consumption of ground beef. To comply with a Food and Drug Administration requirement for approval of enrofloxacin use in dairy heifers, a binomial event tree was constructed following Food and Drug Administration guidance 152. Release was estimated from the slaughter of dairy cattle carrying fluoroquinolone-resistant bacteria attributed to the proposed use in dairy heifers. For exposure, human foodborne exposure to Campylobacter, Salmonella, and MDR Salmonella after consumption of ground beef was estimated. The consequence assessment included illness, fluoroquinolone treatment, and persistent symptoms in patients treated with a fluoroquinolone. Using best available data to estimate the parameters and probabilities of each event, stochastic simulation was used to represent uncertainty and variability in many of the parameters. A scenario analysis was performed to evaluate the uncertainty of the following parameters: (1) probability of resistance development in treated animals, (2) portion of illnesses attributable to ground beef, and (3) probability of persistent symptoms in patients 18 years of age and over treated with a fluoroquinolone. The population at risk was restricted to people 18 years of age and over, as fluoroquinolones are not labeled for treatment of gastroenteritis in children. The mean annual increased risk of cases in the U.S. population (18 years of age and over) where compromised fluoroquinolone treatment resulted in persistent symptoms was estimated to be 1 in 61 billion (one case every 293 years) for Salmonella, 1 in 33 billion (one case every 158 years) for MDR Salmonella, and 1 in 2.8 billion (one case every 13 years) for Campylobacter.

Predictors of the Persistence of Conduct Difficulties in Children with Cognitive Delay

ERIC Educational Resources Information Center

Emerson, Eric; Einfeld, Stewart; Stancliffe, Roger J.

2011-01-01

Background: High rates of conduct difficulties have been reported among children with borderline intellectual disabilities or intellectual disabilities. Little is known about predictors of the persistence of conduct difficulties in the pre-adolescent period in this high-risk group. Methods: Secondary analysis of data from the first three waves of…

The Bumble Bee Flies Anyway: How at Risk 12th Graders Persist to Graduation

ERIC Educational Resources Information Center

Parkin, Suzette T.

2008-01-01

The purpose of this study was to listen to the students' stories and discover why some students in at-risk populations are able to persist in their education and complete their high school graduation requirements despite the odds against their doing so. The findings of this study revealed that students are influenced by a multitude of factors.…

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

PubMed

Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

2017-06-18

Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

PubMed Central

Wilson, Andrew F.; Li, Xue

2017-01-01

ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. PMID:28475398

Recurrent urinary tract infections in healthy and nonpregnant women✩

PubMed Central

Glover, Matthew; Moreira, Cristiano G.; Sperandio, Vanessa; Zimmern, Philippe

2016-01-01

Recurrent urinary tract infections (RUTI) are prevalent and pose significant clinical challenges. Although the term RUTI has long been vaguely defined, a consensus definition has emerged in recent years. The exact etiology behind RUTI remains under debate, with valid arguments for both ascending reinfections as well as persistent infection inside the bladder. These persistent infections exist in the form of quiescent intracellular reservoirs in the mouse model and may represent a novel concept to explain UTI recurrence in humans. Manageable risk factors such as behavioral patterns alongside nonmanageable risk factors including genetic susceptibility are growing fields of investigation. Acute UTI have been studied through two model bacterial strains: Escherichia coli UTI89 and CFT073. However, the clinical relevance to RUTI of these two strains has not been firmly established. Current treatment strategies for RUTI are limited and remain dominated by antibiotic usage despite variable efficacy. The majority of studies in humans have focused on younger groups of women with little information available about the postmenopausal population despite a heightened risk of RUTI in this age group. PMID:27499825

Intrinsic Chemiluminescence Generation during Advanced Oxidation of Persistent Halogenated Aromatic Carcinogens.

PubMed

Mao, Li; Liu, Yu-Xiang; Huang, Chun-Hua; Gao, Hui-Ying; Kalyanaraman, Balaraman; Zhu, Ben-Zhan

2015-07-07

The ubiquitous distribution coupled with their carcinogenicity has raised public concerns on the potential risks to both human health and the ecosystem posed by the halogenated aromatic compounds (XAr). Recently, advanced oxidation processes (AOPs) have been increasingly favored as an "environmentally-green" technology for the remediation of such recalcitrant and highly toxic XAr. Here, we show that AOPs-mediated degradation of the priority pollutant pentachlorophenol and all other XAr produces an intrinsic chemiluminescence that directly depends on the generation of the extremely reactive hydroxyl radicals. We propose that the hydroxyl radical-dependent formation of quinoid intermediates and electronically excited carbonyl species is responsible for this unusual chemiluminescence production. A rapid, sensitive, simple, and effective chemiluminescence method was developed to quantify trace amounts of XAr and monitor their real-time degradation kinetics. These findings may have broad biological and environmental implications for future research on this important class of halogenated persistent organic pollutants.

Spatial heterogeneity in human activities favors the persistence of wolves in agroecosystems.

PubMed

Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad

2014-01-01

As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people.

Spatial Heterogeneity in Human Activities Favors the Persistence of Wolves in Agroecosystems

PubMed Central

Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad

2014-01-01

As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people. PMID:25251567

CONTAMINANT CONCENTRATIONS IN WHOLE-BODY FISH AND SHELLFISH FROM U.S. ESTUARIES

EPA Science Inventory

Persistent bioaccumulative and toxic (PBT) pollutants are chemical contaminants that pose risks to ecosystems and human health. For these reasons, available tissue contaminant data from the US EPA Environmental Monitoring and Assessment Program's National Coastal Assessment were...

DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.

PubMed

Nauwelaërs, Gwendoline; Bellamri, Medjda; Fessard, Valérie; Turesky, Robert J; Langouët, Sophie

2013-09-16

Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25-100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM-10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers.

DNA Adducts of the Tobacco Carcinogens 2-Amino-9H-pyrido[2,3-b]indole and 4-Aminobiphenyl are Formed at Environmental Exposure levels and Persist in Human Hepatocytes

PubMed Central

Nauwelaërs, Gwendoline; Bellamri, Medjda; Fessard, Valérie; Turesky, Robert J.; Langouët, Sophie

2013-01-01

Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25–100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ~5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a ten thousand-fold concentration range (1 nM – 10 µM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes, suggests that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers. PMID:23898916

Long-term persistence of human papillomavirus in the skin of the glans penis of elderly men above 80 years of age.

PubMed

Kitamura, Tadaichi; Suzuki, Motofumi; Koyama, Yasuhiro; Shigehara, Kazuyoshi

2018-05-01

Investigations of human papillomavirus (HPV) in the glans penis are scarce, especially with regard to its natural history. To elucidate HPV prevalence among Japanese men attending urological clinics, 798 adult participants were recruited consecutively and stratified into groups by age based on 10-year intervals. The overall HPV prevalence among the participants was 24.8%, with 15.5% positive for high-risk HPV and 9.3% infected with other HPVs. The HPV positivity rate was sustained in those over 80 years of age at nearly the same level as those in the younger age groups. We also determined the age at last sexual intercourse of 15 HPV-positive participants in the 80+ years age group. In addition, six participants positive for HPV were re-examined for HPV and all showed nearly the same HPV types as those identified in their first examinations. The difference between the age at the first test and the age of last intercourse was 8.3 ± 6.2 years. Except for the elderly group who reported sexual intercourse within the previous year, the duration was 10.0 ± 5.1 years. Our data suggest an HPV persistence of at least eight years. Further investigation is necessary to elucidate the long-term persistence of HPV infection in the glans penis.

Persistent organic pollutants in the natural environments of the city of Bratsk (Irkutsk Oblast): Levels and risk assessment

NASA Astrophysics Data System (ADS)

Mamontova, E. A.; Tarasova, E. N.; Mamontov, A. A.

2014-11-01

The contents of persistent organic pollutants (POPs)—polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)—in the natural environments of an industrial city (Bratsk) of Irkutsk oblast have been studied. Features of the spatial and seasonal distribution of the PCBs and OCPs in the soils and the atmospheric air have been revealed. The structure of the homological and congeneric composition of the PCBs in the soils and the atmospheric air has been shown. Parameters of the carcinogenic and noncarcinogenic risks for human health from the impact of the PCBs and OCPs present in the soils and the atmospheric air have been determined.

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

PubMed

Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus

PubMed Central

Weber de Melo, Vanessa; Sheikh Ali, Hanan; Freise, Jona; Kühnert, Denise; Essbauer, Sandra; Mertens, Marc; Wanka, Konrad M; Drewes, Stephan; Ulrich, Rainer G; Heckel, Gerald

2015-01-01

Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population. PMID:26136821

Re-Emergence of the Apicomplexan Theileria equi in the United States: Elimination of Persistent Infection and Transmission Risk

PubMed Central

Ueti, Massaro W.; Mealey, Robert H.; Kappmeyer, Lowell S.; White, Stephen N.; Kumpula-McWhirter, Nancy; Pelzel, Angela M.; Grause, Juanita F.; Bunn, Thomas O.; Schwartz, Andy; Traub-Dargatz, Josie L.; Hendrickson, Amy; Espy, Benjamin; Guthrie, Alan J.; Fowler, W. Kent; Knowles, Donald P.

2012-01-01

Arthropod-borne apicomplexan pathogens that cause asymptomatic persistent infections present a significant challenge due to their life-long transmission potential. Although anti-microbials have been used to ameliorate acute disease in animals and humans, chemotherapeutic efficacy for apicomplexan pathogen elimination from a persistently infected host and removal of transmission risk is largely unconfirmed. The recent re-emergence of the apicomplexan Theileria equi in U.S. horses prompted testing whether imidocarb dipropionate was able to eliminate T. equi from naturally infected horses and remove transmission risk. Following imidocarb treatment, levels of T. equi declined from a mean of 104.9 organisms/ml of blood to undetectable by nested PCR in 24 of 25 naturally infected horses. Further, blood transfer from treated horses that became nested PCR negative failed to transmit to naïve splenectomized horses. Although these results were consistent with elimination of infection in 24 of 25 horses, T. equi-specific antibodies persisted in the majority of imidocarb treated horses. Imidocarb treatment was unsuccessful in one horse which remained infected as measured by nested PCR and retained the ability to infect a naïve recipient via intravenous blood transfer. However, a second round of treatment eliminated T. equi infection. These results support the utility of imidocarb chemotherapy for assistance in the control and eradication of this tick-borne pathogen. Successful imidocarb dipropionate treatment of persistently infected horses provides a tool to aid the global equine industry by removing transmission risk associated with infection and facilitating international movement of equids between endemic and non-endemic regions. PMID:22970295

Multimatrix measurement of persistent organic pollutants in Mar Chiquita, a continental saline shallow lake.

PubMed

Ballesteros, M L; Miglioranza, K S B; Gonzalez, M; Fillmann, G; Wunderlin, D A; Bistoni, M A

2014-08-15

RAMSAR sites are determined by specific characteristics of the environment in terms of ecological productivity as well services for human development, but they are also one of the most threatened ecosystems. Thus, the objective of this work was to evaluate the dynamic of Persistent Organic Pollutants (POPs) in different biotic and abiotic matrixes of the RAMSAR site (wetlands with international importance), Mar Chiquita Lake. Sampling was performed according to land use (agricultural, urban, and industrial) at two stations: Laguna del Plata and Campo Mare. POPs were analyzed in superficial water (Sw), suspended particulate material (SPM), bottom sediment (Bs) and fish tissues (Odontesthes bonariensis). Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were analyzed by GC-ECD. HCHs, Endosulfans, DDTs, PCBs and PBDEs were found in all matrixes at both stations. The high persistence and transport processes are responsible for the occurrence of HCHs, DDTs and PCBs in Bs, SPM and fish tissues, even many years after their prohibition. PBDEs showed lower levels according to the scarcity of punctual sources in the area. Endosulfan showed variable amounts in agreement with application periods since this pesticide was used until a few years ago in this area. Finally, PCB levels overpassed the acceptable daily intake for human consumption being a risk for human health Thus, the present report confirms the occurrence of POPs in Mar Chiquita lake, alerting on the contribution of agricultural and urban pollutants in a RAMSAR site. Current results also raise concerns on biomagnification processes through the food web. Copyright © 2014 Elsevier B.V. All rights reserved.

Survival of bactericidal antibiotic treatment by tolerant persister cells of Klebsiella pneumoniae.

PubMed

Li, Ying; Zhang, Luhua; Zhou, Yingshun; Zhang, Zhikun; Zhang, Xinzhuo

2018-03-01

Persister cells, a subpopulation of tolerant cells within the bacterial culture, are commonly thought to be responsible for antibiotic therapy failure and infection recurrence. Klebsiella pneumoniae is a notorious human pathogen for its increasing resistance to antibiotics and wide involvement in severe infections. In this study, we aimed to investigate the persister subpopulation of K. pneumoniae. The presence of persisters in K. pneumoniae was determined by treatment with high concentrations of antibiotics, used alone or in combination. The effect of low level of antibiotics on persister formation was investigated by pre-exposure of cells to antibiotics with low concentrations followed by higher doses. The dependence of persister levels on growth phase was determined by measuring the survival ability of cells along the growth stages upon exposure to a high concentration of antibiotic. Analysis on persister type was carried out by persister elimination assays.Results/Key findings. We show that K. pneumoniae produces high levels of tolerant persister cells to survive treatment by a variety of high concentrations of bactericidal antibiotics and persister formation is prevalent among K. pneumoniae clinical strains. Besides, we find that persister cells can be induced by low concentrations of antibiotics. Finally, we provide evidence that persister formation is growth phase-dependent and Type II persisters dominate the persister subpopulation during the entire exponential phase of K. pneumoniae. Our study describes the formation of tolerant persister cells that allow survival of treatment by high concentrations of antibiotics in K. pneumoniae.

Spirituality as a Validating Factor and Intrinsic Motivator to Persistence: A Study of Nontraditional Female Students in Community/Technical Colleges

ERIC Educational Resources Information Center

Jarrell, Camille Laperouse

2009-01-01

While traditional theories are useful in the study of persistence in some nontraditional students, many nontraditional female students are at high risk of not successfully persisting towards their educational goals. The purpose of this study was to explore the perceptions and experiences of spirituality, as a validating factor and an intrinsic…

Commentary: Increased Risk of Later Emotional and Behavioural Problems in Children with SLI -- Reflections on Yew and O'Kearney (2013)

ERIC Educational Resources Information Center

Conti-Ramsden, Gina

2013-01-01

Children with Specific Language Impairment (SLI) find it effortful to learn to talk and these difficulties can be persistent. Given the importance of language to human behaviour, it is not surprising to find that language difficulties are a risk factor for associated difficulties in other aspects of children's development. This article asks…

DOSE-RESPONSE OF PERFLUOROOCTANOIC ACID-INDUCED IMMUNOMODULATION IN ADULT C57BL/6 MICE

EPA Science Inventory

Perfluorooctanoic acid (PFOA), used in fluoropolymer production, is environmentally persistent, present in the human population worldwide, and is associated with myriad health effects under laboratory conditions. A preliminary risk assessment by the US EPA identified immunosuppre...

Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

EPA Science Inventory

Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cas...

Persistent Infection of Human Fetal Endothelial Cells with Rubella Virus

PubMed Central

Perelygina, Ludmila; Zheng, Qi; Metcalfe, Maureen; Icenogle, Joseph

2013-01-01

Cardiovascular abnormalities are the leading cause of neonatal death among patients with congenital rubella syndrome (CRS). Although persistence of rubella virus (RV) in fetal endothelium has been repeatedly suggested as a possible cause of cardiovascular birth defects, evidence of the permissiveness of fetal endothelial cells to RV is lacking. In this study we evaluated the ability of RV to infect and persist in primary fetal endothelial cells derived from human umbilical vein (HUVEC). We found that wild type (wt) low passage clinical RV productively infected HUVEC cultures without producing cytopathology or ultrastructural changes. RV did not inhibit host cell protein synthesis, cell proliferation, or interfere with the cell cycle. Persistently infected cultures were easily established at low and high multiplicities of infection (MOI) with both laboratory and wt clinical RV strains. However, synchronous infections of entire HUVEC monolayers were only observed with clinical RV strains. The release of infectious virions into media remained at consistently high levels for several subcultures of infected HUVEC. The results indicate that macrovascular fetal endothelial cells are highly permissive to RV and allow slow persistent RV replication. The findings provide more evidence for the suggestion that vascular pathologies in CRS are triggered by persistent rubella virus infection of the endothelium. PMID:23940821

Human Leukocyte Antigen Class I and Class II Polymorphisms and Serum Cytokine Profiles in Cervical Cancer.

PubMed

Bahls, Larissa; Yamakawa, Roger; Zanão, Karina; Alfieri, Daniela; Flauzino, Tamires; Delongui, Francieli; de Abreu, André; Souza, Raquel; Gimenes, Fabrícia; Reiche, Edna; Borelli, Sueli; Consolaro, Marcia

2017-08-31

Only a small proportion of women who are exposed to infection with high-risk human papillomavirus (HR-HPV) progress to persistent infection and develop cervical cancer (CC). The immune response and genetic background of the host may affect the risk of progression from a HR-HPV infection to lesions and cancer. However, to our knowledge, no studies has been conducted to evaluate the relationship between variability of human leukocyte antigens ( HLA ) genes and serum cytokine expression in this pathology. In the current study, we examined the associations of HLA alleles and haplotypes including Class I ( HLA-A , -B and -C ) and II ( HLA-DRB1 , -DQA1 and -DQB1 ) with serum levels of cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10 and IL-17 as well as risks of HPV infections, lesions and CC among admixed Brazilian women. HLA polymorphisms were associated with an increased risk or protection from HPV, lesions and CC. Additionally, we demonstrated a potential association of a HLA class I haplotype ( HLA-B*14-C*08 ) with higher IL-10 cytokine serum levels in cervical disease, suggesting an association between HLA class I and specific cytokines in cervical carcinogenesis. However, larger studies with detailed HPV types coupled with genetic data are needed to further evaluate the effects of HLA and CC by HPV genotype.

Human Leukocyte Antigen Class I and Class II Polymorphisms and Serum Cytokine Profiles in Cervical Cancer

PubMed Central

Bahls, Larissa; Yamakawa, Roger; Zanão, Karina; Alfieri, Daniela; Flauzino, Tamires; Delongui, Francieli; de Abreu, André; Souza, Raquel; Gimenes, Fabrícia; Reiche, Edna; Borelli, Sueli; Consolaro, Marcia

2017-01-01

Only a small proportion of women who are exposed to infection with high-risk human papillomavirus (HR-HPV) progress to persistent infection and develop cervical cancer (CC). The immune response and genetic background of the host may affect the risk of progression from a HR-HPV infection to lesions and cancer. However, to our knowledge, no studies has been conducted to evaluate the relationship between variability of human leukocyte antigens (HLA) genes and serum cytokine expression in this pathology. In the current study, we examined the associations of HLA alleles and haplotypes including Class I (HLA-A, -B and -C) and II (HLA-DRB1, -DQA1 and -DQB1) with serum levels of cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10 and IL-17 as well as risks of HPV infections, lesions and CC among admixed Brazilian women. HLA polymorphisms were associated with an increased risk or protection from HPV, lesions and CC. Additionally, we demonstrated a potential association of a HLA class I haplotype (HLA-B*14-C*08) with higher IL-10 cytokine serum levels in cervical disease, suggesting an association between HLA class I and specific cytokines in cervical carcinogenesis. However, larger studies with detailed HPV types coupled with genetic data are needed to further evaluate the effects of HLA and CC by HPV genotype. PMID:28858203

Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study

PubMed Central

Pirtea, Laurențiu; Grigoraş, Dorin; Matusz, Petru; Pirtea, Marilena; Moleriu, Lavinia; Tudor, Anca; Ilina, Răzvan; Secoşan, Cristina; Mazilu, Octavian

2016-01-01

Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related. Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP. Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only. Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate. PMID:27366164

Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns

PubMed Central

Lewis, Maria E.; Belland, Robert J.; AbdelRahman, Yasser M.; Beatty, Wandy L.; Aiyar, Ashok A.; Zea, Arnold H.; Greene, Sheila J.; Marrero, Luis; Buckner, Lyndsey R.; Tate, David J.; McGowin, Chris L.; Kozlowski, Pamela A.; O'Brien, Michelle; Lillis, Rebecca A.; Martin, David H.; Quayle, Alison J.

2014-01-01

In vitro models of Chlamydia trachomatis growth have long been studied to predict growth in vivo. Alternative or persistent growth modes in vitro have been shown to occur under the influence of numerous stressors but have not been studied in vivo. Here, we report the development of methods for sampling human infections from the endocervix in a manner that permits a multifaceted analysis of the bacteria, host and the endocervical environment. Our approach permits evaluating total bacterial load, transcriptional patterns, morphology by immunofluorescence and electron microscopy, and levels of cytokines and nutrients in the infection microenvironment. By applying this approach to two pilot patients with disparate infections, we have determined that their contrasting growth patterns correlate with strikingly distinct transcriptional biomarkers, and are associated with differences in local levels of IFNγ. Our multifaceted approach will be useful to dissect infections in the human host and be useful in identifying patients at risk for chronic disease. Importantly, the molecular and morphological analyses described here indicate that persistent growth forms can be isolated from the human endocervix when the infection microenvironment resembles the in vitro model of IFNγ-induced persistence. PMID:24959423

The art of persistence-the secrets to Burkholderia chronic infections.

PubMed

Lewis, Eric R G; Torres, Alfredo G

2016-08-01

The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Unusual dynamics of extinction in a simple ecological model.

PubMed Central

Sinha, S; Parthasarathy, S

1996-01-01

Studies on natural populations and harvesting biological resources have led to the view, commonly held, that (i) populations exhibiting chaotic oscillations run a high risk of extinction; and (ii) a decrease in emigration/exploitation may reduce the risk of extinction. Here we describe a simple ecological model with emigration/depletion that shows behavior in contrast to this. This model displays unusual dynamics of extinction and survival, where populations growing beyond a critical rate can persist within a band of high depletion rates, whereas extinction occurs for lower depletion rates. Though prior to extinction at lower depletion rates the population exhibits chaotic dynamics with large amplitudes of variation and very low minima, at higher depletion rates the population persists at chaos but with reduced variation and increased minima. For still higher values, within the band of persistence, the dynamics show period reversal leading to stability. These results illustrate that chaos does not necessarily lead to population extinction. In addition, the persistence of populations at high depletion rates has important implications in the considerations of strategies for the management of biological resources. PMID:8643661

Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.

PubMed

Mattes, F M; Vargas, A; Kopycinski, J; Hainsworth, E G; Sweny, P; Nebbia, G; Bazeos, A; Lowdell, M; Klenerman, P; Phillips, R E; Griffiths, P D; Emery, V C

2008-05-01

Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.

Predictors of persistent maternal depression trajectories in early childhood: results from the EDEN mother-child cohort study in France.

PubMed

van der Waerden, J; Galéra, C; Saurel-Cubizolles, M-J; Sutter-Dallay, A-L; Melchior, M

2015-07-01

Maternal depression in the pre- and postpartum period may set women on a course of chronic depressive symptoms. Little is known about predictors of persistently elevated depressive symptoms in mothers from pregnancy onwards. The aims of this study are to determine maternal depression trajectories from pregnancy to the child's fifth birthday and identify associated risk factors. Mothers (N = 1807) from the EDEN mother-child birth cohort study based in France (2003-2011) were followed from 24-28 weeks of pregnancy to their child's fifth birthday. Maternal depression trajectories were determined with a semi-parametric group-based modelling strategy. Sociodemographic, psychosocial and psychiatric predictors were explored for their association with trajectory class membership. Five trajectories of maternal symptoms of depression from pregnancy onwards were identified: no symptoms (60.2%); persistent intermediate-level depressive symptoms (25.2%); persistent high depressive symptoms (5.0%); high symptoms in pregnancy only (4.7%); high symptoms in the child's preschool period only (4.9%). Socio-demographic predictors associated with persistent depression were non-French origin; psychosocial predictors were childhood adversities, life events during pregnancy and work overinvestment; psychiatric predictors were previous mental health problems, psychological help, and high anxiety during pregnancy. Persistent depression in mothers of young children is associated to several risk factors present prior to or during pregnancy, notably anxiety. These characteristics precede depression trajectories and offer a possible entry point to enhance mother's mental health and reduce its burden on children.

Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure

PubMed Central

Nicklisch, Sascha C. T.; Rees, Steven D.; McGrath, Aaron P.; Gökirmak, Tufan; Bonito, Lindsay T.; Vermeer, Lydia M.; Cregger, Cristina; Loewen, Greg; Sandin, Stuart; Chang, Geoffrey; Hamdoun, Amro

2016-01-01

The world’s oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed. Although it is well known that these pollutants are potentially hazardous to human and environmental health, their impacts remain incompletely understood. We examined how persistent organic pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an evolutionarily conserved defense protein that is essential for protection against environmental toxicants. We identified specific congeners of organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers that inhibit mouse and human P-gp, and determined their environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we solved the cocrystal structure of P-gp bound to one of these inhibitory pollutants, PBDE (polybrominated diphenyl ether)–100, providing the first view of pollutant binding to a drug transporter. The results demonstrate the potential for specific binding and inhibition of mammalian P-gp by ubiquitous congeners of persistent organic pollutants present in fish and other foods, and argue for further consideration of transporter inhibition in the assessment of the risk of exposure to these chemicals. PMID:27152359

Climate change in metacommunities: dispersal gives double-sided effects on persistence.

PubMed

Eklöf, Anna; Kaneryd, Linda; Münger, Peter

2012-11-05

Climate change is increasingly affecting the structure and dynamics of ecological communities both at local and at regional scales, and this can be expected to have important consequences for their robustness and long-term persistence. The aim of the present work is to analyse how the spatial structure of the landscape and dispersal patterns of species (dispersal rate and average dispersal distance) affects metacommunity response to two disturbances: (i) increased mortality during dispersal and (ii) local species extinction. We analyse the disturbances both in isolation and in combination. Using a spatially and dynamically explicit metacommunity model, we find that the effect of dispersal on metacommunity persistence is two-sided: on the one hand, high dispersal significantly reduces the risk of bottom-up extinction cascades following the local removal of a species; on the other hand, when dispersal imposes a risk to the dispersing individuals, high dispersal increases extinction risks, especially when dispersal is global. Large-bodied species with long generation times at the highest trophic level are particularly vulnerable to extinction when dispersal involves a risk. This suggests that decreasing the mortality risk of dispersing individuals by improving the quality of the habitat matrix may greatly increase the robustness of metacommunities.

Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment.

PubMed

Nowak, Karolin; Linzner, Daniela; Thrasher, Adrian J; Lambert, Paul F; Di, Wei-Li; Burns, Siobhan O

2017-10-01

Loss-of-function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency characterized by lack of T and natural killer cells and infant death from infection. Hematopoietic stem cell transplantation or gene therapy offer a cure, but despite successful replacement of lymphoid immune lineages, a long-term risk of severe cutaneous human papilloma virus infections persists, possibly related to persistent γc-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional γc and its co-receptors. After stimulation with the γc-ligand IL-15, γc-deficient keratinocytes show significantly impaired secretion of specific chemokines including CXCL1, CXCL8, and CCL20, resulting in reduced chemotaxis of dendritic cells and CD4 + T cells. Furthermore, γc-deficient keratinocytes also exhibit defective induction of T-cell chemotaxis in a model of stable human papilloma virus-18 infection. These findings suggest that persistent γc-deficiency in keratinocytes alters immune cell recruitment to the skin, which may contribute to the development and persistence of warts in this condition and would require different treatment approaches. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human error mitigation initiative (HEMI) : summary report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Susan M.; Ramos, M. Victoria; Wenner, Caren A.

2004-11-01

Despite continuing efforts to apply existing hazard analysis methods and comply with requirements, human errors persist across the nuclear weapons complex. Due to a number of factors, current retroactive and proactive methods to understand and minimize human error are highly subjective, inconsistent in numerous dimensions, and are cumbersome to characterize as thorough. An alternative and proposed method begins with leveraging historical data to understand what the systemic issues are and where resources need to be brought to bear proactively to minimize the risk of future occurrences. An illustrative analysis was performed using existing incident databases specific to Pantex weapons operationsmore » indicating systemic issues associated with operating procedures that undergo notably less development rigor relative to other task elements such as tooling and process flow. Future recommended steps to improve the objectivity, consistency, and thoroughness of hazard analysis and mitigation were delineated.« less

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.

PubMed

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-09-03

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of 'supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.

Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.

PubMed

Rodríguez, Ana Cecilia; Schiffman, Mark; Herrero, Rolando; Hildesheim, Allan; Bratti, Concepción; Sherman, Mark E; Solomon, Diane; Guillén, Diego; Alfaro, Mario; Morales, Jorge; Hutchinson, Martha; Katki, Hormuzd; Cheung, Li; Wacholder, Sholom; Burk, Robert D

2010-03-03

The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (> or =42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse. The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

ENDOCRINE DISRUPTING CHEMICAL RISK MANAGEMENT RESEARCH IN THE US EPA'S OFFICE OF RESEARCH AND DEVELOPMENT

EPA Science Inventory

Endocrine disrupting chemicals (EDCs) are receiving increasing media and scientific attention. Concerns about these chemicals stem from the possibility of serious human and wildlife effects and environmental persistence. The US EPA Office of Research and Development's National ...

TRACKING CHLORDANE COMPOSITIONAL AND CHIRAL PROFILES IN SOIL AND VEGETATION. (R828174)

EPA Science Inventory

The cycling of chlordane and other persistent organic pollutants through the environment must be comprehensively elucidated to assess adequately the human health risks posed from such contaminants. In this study the compositional and chiral profiles of weathered chlordane resi...

Quantitative trait loci (QTL) analysis of PCB126 induced developmental toxicity in zebrafish

EPA Science Inventory

Polychlorinated dioxins and biphenyls are potent developmental toxicants which persist in the environment and pose risk to ecological and human health. Variation in susceptibility to this class of compounds has been demonstrated within and among several piscine, avian and mammali...

Ketamine and the metabolite norketamine: persistence and phototransformation toxicity in hospital wastewater and surface water.

PubMed

Lin, Angela Yu-Chen; Lee, Wan-Ning; Wang, Xiao-Huan

2014-04-15

Ketamine has been increasingly used both recreationally and medicinally around the world. Although the metabolic pathways to form its metabolite norketamine have been carefully investigated in humans and animals, knowledge of their environmental occurrence and fate is limited. In this study, we investigated the occurrence of ketamine and norketamine in 20 natural bodies of water, effluents from 13 hospitals, two wastewater treatment plants and one water supply plant. Ketamine was found at concentrations as high as 10 μg/L. Ketamine and norketamine were consistently found in similar concentrations (ketamine/norketamine ratio: 0.3-4.6) in the collected water samples, and this ratio similar to that found in urine samples. Dark incubation experiments have shown that ketamine is not susceptible to microbial degradation or hydrolysis. Phototransformation was demonstrated to significantly reduce the concentration of ketamine and norketamine in river waters (t(1/2) = 12.6 ± 0.4 and 10.1 ± 0.4 h, respectively) and resulted in byproducts that are similar to human metabolites. Both direct and indirect photolysis led to the N-demethylation of ketamine to form norketamine and other byproducts, including hydroxy-norketamine (HNK), dehydronorketamine (DNK), hydroxy-ketamine (HK) and isomer forms of ketamine and norketamine. Irradiated solutions exhibited higher toxicity (via the Microtox test). Although a final risk assessment could not be made due to a lack of studies on the chronic effects on aquatic organisms, the high and persistent environmental occurrences of ketamine and norketamine as well as the increasingly acute toxicity of the photo byproducts demonstrate the importance of including metabolites in evaluation of the overall risk of ketamine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice

PubMed Central

Park, Soyeong; Park, Jung Wook; Pitot, Henry C.

2016-01-01

ABSTRACT   Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. Importance   Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients. PMID:27190216

Loss of Dependence on Continued Expression of the Human Papillomavirus 16 E7 Oncogene in Cervical Cancers and Precancerous Lesions Arising in Fanconi Anemia Pathway-Deficient Mice.

PubMed

Park, Soyeong; Park, Jung Wook; Pitot, Henry C; Lambert, Paul F

2016-05-17

Fanconi anemia (FA) is a rare genetic disorder caused by defects in DNA damage repair. FA patients often develop squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) are known to cause cancer, including the cervix. However, SCCs found in human FA patients are often HPV negative, even though the majority of female FA patients with anogenital cancers had preexisting HPV-positive dysplasia. We hypothesize that HPVs contribute to the development of SCCs in FA patients but that the continued expression of HPV oncogenes is not required for the maintenance of the cancer state because FA deficiency leads to an accumulation of mutations in cellular genes that render the cancer no longer dependent upon viral oncogenes. We tested this hypothesis, making use of Bi-L E7 transgenic mice in which we temporally controlled expression of HPV16 E7, the dominant viral oncogene in HPV-associated cancers. As seen before, the persistence of cervical neoplastic disease was highly dependent upon the continued expression of HPV16 E7 in FA-sufficient mice. However, in mice with FA deficiency, cervical cancers persisted in a large fraction of the mice after HPV16 E7 expression was turned off, indicating that these cancers had escaped from their dependency on E7. Furthermore, the severity of precancerous lesions also failed to be reduced significantly in the mice with FA deficiency upon turning off expression of E7. These findings confirm our hypothesis and may explain the fact that, while FA patients have a high frequency of infections by HPVs and HPV-induced precancerous lesions, the cancers are frequently HPV negative. IMPORTANCE  : Fanconi anemia (FA) patients are at high risk for developing squamous cell carcinoma (SCC) at sites where high-risk human papillomaviruses (HPVs) frequently cause cancer. Yet these SCCs are often HPV negative. FA patients have a genetic defect in their capacity to repair damaged DNA. HPV oncogenes cause an accumulation of DNA damage. We hypothesize, therefore, that DNA damage induced by HPV leads to an accumulation of mutations in patients with FA deficiency and that such mutations allow HPV-driven cancers to become independent of the viral oncogenes. Consistent with this hypothesis, we found that cervical cancers arising in HPV16 transgenic mice with FA deficiency frequently escape from dependency on the HPV16 oncogene that drove its development. Our report provides further support for vaccination of FA patients against HPVs and argues for the need to define mutational profiles of SCCs arising in FA patients in order to inform precision medicine-based approaches to treating these patients. Copyright © 2016 Park et al.

Stigma and Human Rights Abuses against People Who Inject Drugs in Russia—A Qualitative Investigation to Inform Policy and Public Health Strategies

PubMed Central

Raj, Anita; Samet, Jeffrey H.

2015-01-01

Introduction Drug policing practices in the Russian Federation (Russia) are often punitive and have been shown to be associated with HIV risk behaviors among people who inject drugs (PWID). Less is known about strategies to address the problem in that setting, where substance use stigma is highly persistent. A better understanding of forms, causes and consequences of drug policing in Russia could inform drug policy in a context of substantial policy resistance. This qualitative study’s goal is to characterize the phenomenon of police involvement with Russian PWID and to explore strategies for drug policing in the Russian country context. Methods Using a semi-structured interview guide, we collected data from a purposive sample of 23 key informants including PWID, police officers, and experts from civil society and international organizations in Russia. We used a thematic analysis approach to inductively generate new insight into the phenomenon of police involvement and potential strategies to address it. Results Policing practices involving PWID include unjustified arrests, planting of false evidence and extrajudicial syringe confiscations, and often constitute human rights violations. Russian PWID personally experienced police violence as ubiquitous, taking on various forms such as beating, unjustified arrests, verbal harassment, and coercion. The persistent societal stigma dehumanizes PWID, and such stigmatization facilitates police abuse. To address stigma and overcome the PWID-police adversity, study participants suggested fostering a mutual understanding between the police and public health sectors. Conclusions Participants describe substantial human rights violations as part of policing illicit drug use in Russia. Police should include principles of effective prevention of substance use and HIV risk reduction in their trainings. Alignment of public safety and public health goals could address drug use-related risks and HIV prevention among key populations in Russia. PMID:26305697

Paradoxical Understandings Regarding Adult Undergraduate Persistence

ERIC Educational Resources Information Center

Kasworm, Carol E.

2014-01-01

Historically, characteristics of student persistence and graduation completion were most often linked to strategies which honored the full-time residential younger undergraduate. Adult students have been viewed as high-risk and typically problematic students for continuous enrollment and degree completion. This article explores the key paradoxical…

Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats.

PubMed

Clark, Robert E; Kuczenski, Ronald; Segal, David S

2007-07-01

Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.

Metabolism and metabolites of polychlorinated biphenyls (PCBs)

PubMed Central

Grimm, FA; Hu, D; Kania-Korwel, I; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

2015-01-01

The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed. PMID:25629923

The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review.

PubMed

Yu, Hainan; Randhawa, Kristi; Côté, Pierre; Optima Collaboration

2016-07-01

Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of physical agents for the management of lower-limb soft tissue injuries had a high risk of bias. High-quality RCTs are still needed to assess the effectiveness of physical agents for managing the broad range of lower-limb soft tissue injuries. The effectiveness of most interventions remains unclear. Level of Evidence Therapy, 1a. Protocol registered July 10, 2014 with PROSPERO (CRD42014010621). J Orthop Sports Phys Ther 2016;46(7):523-554. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6521.

Persistent increases in inflammatory cytokines, Akt, and MAPK/ERK pathways after inhalation exposure of rats to Libby amphibole (LA) or amosite: comparison to effects after intratracheal exposure to LA or naturally occurring asbestos.

EPA Science Inventory

Human exposure to LA and other mined or processed asbestos increases risk of lung inflammation, fibrosis, and cancer. Health risks from exposure to naturally occurring asbestos (NOA) are not as well-understood. Mechanisms of long-term toxicity were compared in male F344 rats expo...

The rise of ampicillin-resistant Enterococcus faecium high-risk clones as a frequent intestinal colonizer in oncohaematological neutropenic patients on levofloxacin prophylaxis: a risk for bacteraemia?

PubMed

Sánchez-Díaz, A M; Cuartero, C; Rodríguez, J D; Lozano, S; Alonso, J M; Rodríguez-Domínguez, M; Tedim, A P; Del Campo, R; López, J; Cantón, R; Ruiz-Garbajosa, P

2016-01-01

Levofloxacin extended prophylaxis (LEP), recommended in oncohaematological neutropenic patients to reduce infections, might select resistant bacteria in the intestine acting as a source of endogenous infection. In a prospective observational study we evaluated intestinal emergence and persistence of ampicillin-resistant Enterococcus faecium (AREfm), a marker of hospital adapted high-risk clones. AREfm was recovered from the faeces of 52 patients with prolonged neutropenia after chemotherapy, at admission (Basal), during LEP, and twice weekly until discharge (Pos-LEP). Antibiotic susceptibility, virulence traits and population structure (pulsed-field gel electrophoresis and multilocus sequence typing) were determined and compared with bacteraemic isolates. Gut enterococcal population was monitored using a quantitative PCR quantification approach. AREfm colonized 61.4% of patients (194/482 faecal samples). Sequential AREfm acquisition (25% Basal, 36.5% LEP, 50% Pos-LEP) and high persistent colonization rates (76.9-89.5%) associated with a decrease in clonal diversity were demonstrated. Isolates were clustered into 24 PFGE-patterns within 13 sequence types, 95.8% of them belonging to hospital-associated Bayesian analysis of population structure subgroups 2.1a and 3.3a. Levofloxacin resistance and high-level streptomycin resistance were a common trait of these high-risk clones. AREfm-ST117, the most persistent clone, was dominant (60.0% isolates, 32.6% patients). It presented esp gene and caused 18.2% of all bacteraemia episodes in 21% of patients previously colonized by this clone. In AREfm-colonized patients, intestinal enrichment in the E. faecium population with a decline in total bacterial load was observed. AREfm intestinal colonization increases during hospital stay and coincides with enterococci population enrichment in the gut. Dominance and intestinal persistence of the ST117 clone might increase the risk of bacteraemia. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chronic pain, body mass index and cardiovascular disease risk factors: tests of moderation, unique and shared relationships in the Study of Women's Health Across the Nation (SWAN).

PubMed

Burns, John W; Quartana, Phillip J; Bruehl, Stephen; Janssen, Imke; Dugan, Sheila A; Appelhans, Bradley; Matthews, Karen A; Kravitz, Howard M

2015-04-01

Chronic pain may be related to cardiovascular disease (CVD) risk. The current study examined whether persistent bodily pain was related to cardiovascular disease risk factors, whether these effects were moderated by body mass index (BMI), and, if not, whether chronic pain accounted for unique variance in CVD risk factors. Participants were women (N = 2,135) in the Study of Women's Health Across the Nation. A high pain frequency variable (high pain in 0 through 4 assessments) was coded to reflect the frequency of high levels of bodily pain across the first 3 years of the study. Six CVD risk factors and BMI were measured at follow-up year 3. High pain frequency and BMI were correlated significantly with risk factors, although effects for the former were small. Hierarchical multiple regressions revealed high pain frequency × BMI interactions for 5 of 6 CVD risk factors. Dissecting the interactions revealed a similar pattern across 4 risk factors: for women with normal BMI, there was a "dose-response" in which increasing frequency of high pain revealed increasingly worse CVD risk factor levels, whereas for women with obese BMI, high pain frequency was unrelated to risk factors. For obese women, increasing frequency of high pain was associated with higher blood glucose. Although BMI is a well-established CVD risk factor, evaluation of CVD risk level may be improved by considering the incidence of persistent pain, particularly in normal weight women (BMI < 25 kg/m(2)) lower BMI.

Screening of pregnant women for hepatitis B.

PubMed

Boxall, E

1998-11-01

Neonatal infection with hepatitis B virus carries a very high risk of resulting in a persistent infection. Babies born to hepatitis B carrier mothers are at risk of infection through exposure to blood and body fluids during birth. These 'at risk' babies can only be identified through screening of all mothers during pregnancy. Prevention of infection in this group is a key element in any nation's strategy to reduce the incidence and eventually eliminate hepatitis B infection in its population as the persistently infected infants are a reservoir of infection throughout their lives. The infected adult carries a relatively low risk of becoming a chronic carrier (< 10%). Various strategies for screening in pregnancy have been adopted. These include attempts to identify women with a history of 'risk behaviour', testing only women who were born in areas of high endemicity, pooling of sera and universal antenatal screening. The advantages and disadvantages of the various strategies will be discussed.

Risk Score Algorithm for Treatment of Persistent Apical Periodontitis

PubMed Central

Yu, V.S.; Khin, L.W.; Hsu, C.S.; Yee, R.; Messer, H.H.

2014-01-01

Persistent apical periodontitis related to a nonvital tooth that does not resolve following root canal treatment may be compatible with health and may not require further intervention. This research aimed to develop a Deterioration Risk Score (DRS) to differentiate lesions requiring further intervention from lesions likely to be compatible with health. In this cross-sectional study, patient records (2003-2008) were screened for root-filled teeth with periapical radiolucency visible on periapical radiographs taken at treatment and at recruitment at least 4 yr later. The final sample consisted of 228 lesions in 182 patients. Potential demographic and treatment risk factors were screened against 3 categorical outcomes (improved/unchanged/deteriorated), and a multivariate independent multinomial probit regression model was built. A 5-level DRS was constructed by summing values of adjusted regression coefficients in the model, based on predicted probabilities of deterioration. Most lesions (127, 55.7%) had improved over time, while 32 (14.0%) remained unchanged, and 69 (30.3%) had deteriorated. Significant predictors of deterioration were as follows: time since treatment (relative risk [RR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, p = .030, rounded beta value = 1, for every year increase after 4 yr), current pain (RR: 3.79, 95% CI: 1.48-9.70, p = .005, rounded beta value = 13), sinus tract present (RR: 4.13, 95% CI: 1.11-15.29, p = .034, rounded beta value = 14), and lesion size (RR: 7.20, 95% CI: 3.70-14.02, p < .001, rounded beta value = 20). Persistent apical periodontitis with DRS <15 represented very low risk; 15-20, low risk; 21-30, moderate risk; 31-40, high risk; and >40, very high risk. DRS could help the clinician identify persistent apical periodontitis at low risk for deterioration, and it would not require intervention. When validated, this tool could reduce the risk of overtreatment and contribute toward targeted care and better efficiency in the timely management of disease. PMID:25190267

Persistent Effects of Libby Amphibole and Amosite Asbestos Following Subchronic Inhalation in Rats

EPA Science Inventory

Background: Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following...

Legionella and Mycobacterium Occurrence/Persistence in Homes and Office Buildings

EPA Science Inventory

Legionella and non-tuberculous Mycobacterium species are two of the more important environmental pathogens that cause human health effects. They contribute to the highest economic burden and one of the heaviest disease burdens of all of the waterborne pathogens that pose a risk t...

A Socio-Environmental Case for Skill in Outdoor Adventure

ERIC Educational Resources Information Center

Mullins, Philip M.

2014-01-01

In response to the crisis of sustainability, this paper revisits understandings of human--environment relations established through skill-based outdoor activities that are used commonly among adventure recreation, education, and tourism. Reconsidering a predominant focus on risk and a persistent tension between technical and environmental…

Oil prices and long-run risk

NASA Astrophysics Data System (ADS)

Ready, Robert Clayton

I show that relative levels of aggregate consumption and personal oil consumption provide an excellent proxy for oil prices, and that high oil prices predict low future aggregate consumption growth. Motivated by these facts, I add an oil consumption good to the long-run risk model of Bansal and Yaron [2004] to study the asset pricing implications of observed changes in the dynamic interaction of consumption and oil prices. Empirically I observe that, compared to the first half of my 1987--2010 sample, oil consumption growth in the last 10 years is unresponsive to levels of oil prices, creating an decrease in the mean-reversion of oil prices, and an increase in the persistence of oil price shocks. The model implies that the change in the dynamics of oil consumption generates increased systematic risk from oil price shocks due to their increased persistence. However, persistent oil prices also act as a counterweight for shocks to expected consumption growth, with high expected growth creating high expectations of future oil prices which in turn slow down growth. The combined effect is to reduce overall consumption risk and lower the equity premium. The model also predicts that these changes affect the riskiness of of oil futures contracts, and combine to create a hump shaped term structure of oil futures, consistent with recent data.

Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

PubMed

Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

2015-08-01

High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification bias. © 2015 American Society for Nutrition.

Longitudinal assessment of high blood pressure in children with nonalcoholic fatty liver disease.

PubMed

Schwimmer, Jeffrey B; Zepeda, Anne; Newton, Kimberly P; Xanthakos, Stavra A; Behling, Cynthia; Hallinan, Erin K; Donithan, Michele; Tonascia, James

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD. Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks. Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05). In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD.

Longitudinal Assessment of High Blood Pressure in Children with Nonalcoholic Fatty Liver Disease

PubMed Central

Schwimmer, Jeffrey B.; Zepeda, Anne; Newton, Kimberly P.; Xanthakos, Stavra A.; Behling, Cynthia; Hallinan, Erin K.; Donithan, Michele; Tonascia, James

2014-01-01

Objective Nonalcoholic fatty liver disease (NAFLD) affects 9.6% of children and may put these children at elevated risk of high blood pressure and subsequent cardiovascular morbidity and mortality. Therefore, we sought to determine the prevalence of and risk factors for high blood pressure in children with NAFLD. Methods Cohort study performed by the NIDDK NASH Clinical Research Network. There were 484 children with NAFLD ages 2 to 17 at enrollment; 382 children were assessed both at enrollment and 48 weeks afterwards. The main outcomes were high blood pressure at baseline and persistent high blood pressure at both baseline and 48 weeks. Results Prevalence of high blood pressure at baseline was 35.8% and prevalence of persistent high blood pressure was 21.4%. Children with high blood pressure were significantly more likely to have worse steatosis than children without high blood pressure (mild 19.8% vs. 34.2%, moderate 35.0% vs. 30.7%, severe 45.2% vs. 35.1%; P = 0.003). Higher body mass index, low-density lipoprotein, and uric acid were independent risk factors for high blood pressure (Odds Ratios: 1.10 per kg/m2, 1.09 per 10 mg/dL, 1.25 per mg/dL, respectively). Compared to boys, girls with NAFLD were significantly more likely to have persistent high blood pressure (28.4% vs.18.9%; P = 0.05). Conclusions In conclusion, NAFLD is a common clinical problem that places children at substantial risk for high blood pressure, which may often go undiagnosed. Thus blood pressure evaluation, control, and monitoring should be an integral component of the clinical management of children with NAFLD. PMID:25419656

The influence of temperature on mortality and its Lag effect: a study in four Chinese cities with different latitudes.

PubMed

Bao, Junzhe; Wang, Zhenkun; Yu, Chuanhua; Li, Xudong

2016-05-04

Global climate change is one of the most serious environmental issues faced by humanity, and the resultant change in frequency and intensity of heat waves and cold spells could increase mortality. The influence of temperature on human health could be immediate or delayed. Latitude, relative humidity, and air pollution may influence the temperature-mortality relationship. We studied the influence of temperature on mortality and its lag effect in four Chinese cities with a range of latitudes over 2008-2011, adjusting for relative humidity and air pollution. We recorded the city-specific distributions of temperature and mortality by month and adopted a Poisson regression model combined with a distributed lag nonlinear model to investigate the lag effect of temperature on mortality. We found that the coldest months in the study area are December through March and the hottest months are June through September. The ratios of deaths during cold months to hot months were 1.43, 1.54, 1.37 and 1.12 for the cities of Wuhan, Changsha, Guilin and Haikou, respectively. The effects of extremely high temperatures generally persisted for 3 days, whereas the risk of extremely low temperatures could persist for 21 days. Compared with the optimum temperature of each city, at a lag of 21 days, the relative risks (95 % confidence interval) of extreme cold temperatures were 4.78 (3.63, 6.29), 2.38 (1.35, 4.19), 2.62 (1.15, 5.95) and 2.62 (1.44, 4.79) for Wuhan, Changsha, Guilin and Haikou, respectively. The respective risks were 1.35 (1.18, 1.55), 1.19 (0.96, 1.48), 1.22 (0.82, 1.82) and 2.47 (1.61, 3.78) for extreme hot temperatures, at a lag of 3 days. Temperature-mortality relationships vary among cities at different latitudes. Local governments should establish regional prevention and protection measures to more effectively confront and adapt to local climate change. The effects of hot temperatures predominantly occur over the short term, whereas those of cold temperatures can persist for an extended number of days.

Human papillomavirus and Chlamydia trachomatis infection in gyneco-obstetric outpatients from a mexican hospital.

PubMed

Conde-Ferráez, Laura; Martíez, Jorge Ramiro Carrillo; Ayora-Talavera, Guadalupe; Losa, María Del Refugio González

2017-01-01

Human papillomavirus (HPV) and Chlamydia trachomatis are the most frequent sexually transmitted infections, usually asymptomatic. Persistent infection with high-risk HPV types and other cofactors such as the concomitant infection with C. trachomatis can represent a higher risk to develop cervical lesions; therefore, screening with sensitive methods could aid to identify women at risk. The aim is to determine the prevalence and concurrence of both infections, detected with in-house molecular methods, and to identify the risk factors associated to the infections in Mexican women. This was a cross-sectional study including gynaecological-obstetrical medical outpatients from a Social Security Hospital in Southeast Mexico. After informed consent, cervicovaginal samples were collected and tested for HPV and C. trachomatis using polymerase chain reaction (PCR). HPV positives were further tested for high-risk HPV16, 18, 58 and low-risk 11 using real-time PCR. All methods employed were in-house. Data analyses included odds ratios (OR), Chi-square and linear regressions. Women included were 233, aging 15-49 (mean 30 years), 52.8% were pregnant. For HPV and C. trachomatis testing, 230 samples were adequate, resulting in 48 (20.9%) and 15 (6.5%) positives, respectively; 4 (1.7%) were positive to both. The most frequent genotype identified was HPV58 (25% of typified samples). C. trachomatis positives were 73% asymptomatic, none had pelvic inflammatory disease or infertility histories. The only variable associated to HPV infection was the history of previous sexually transmitted disease (OR = 3.69,P= 0.0019). More than 25% of the population was infected with either agent. We successfully used in-house molecular methodologies for diagnosis and typing, showing HPV and C. trachomatis prevalence consistent to previous reports. Concomitant infections were found, HPV high-risk types were involved in half of these cases, representing a higher risk.

Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

PubMed

Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

2017-01-01

Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age.

PubMed

Lowe, Adrian J; Angelica, Bianca; Su, John; Lodge, Caroline J; Hill, David J; Erbas, Bircan; Bennett, Catherine M; Gurrin, Lyle C; Axelrad, Christine; Abramson, Michael J; Allen, Katrina J; Dharmage, Shyamali C

2017-06-01

Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Increased receptor for advanced glycation end product expression in the human alcoholic prefrontal cortex is linked to adolescent drinking.

PubMed

Vetreno, Ryan P; Qin, Liya; Crews, Fulton T

2013-11-01

Adolescence is characterized behaviorally by increased impulsivity and risk-taking that declines in parallel with maturation of the prefrontal cortex and executive function. In the brain, the receptor for advanced glycation end products (RAGE) is critically involved in neurodevelopment and neuropathology. In humans, the risk of alcoholism is greatly increased in those who begin drinking between 13 and 15years of age, and adolescents binge drink more than any other age group. We have previously found that alcoholism is associated with increased expression of neuroimmune genes. This manuscript tested the hypothesis that adolescent binge drinking upregulates RAGE and Toll-like receptor (TLR) 4 as well as their endogenous agonist, high-mobility group box 1 (HMGB1). Immunohistochemistry, Western blot, and mRNA analyses found that RAGE expression was increased in the human post-mortem alcoholic orbitofrontal cortex (OFC). Further, an earlier age of drinking onset correlated with increased expression of RAGE, TLR4, and HMGB1. To determine if alcohol contributed to these changes, we used an adolescent binge ethanol model in rats (5.0g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) and assessed neuroimmune gene expression. We found an age-associated decline of RAGE expression from late adolescence (P56) to young adulthood (P80). Adolescent intermittent ethanol exposure did not alter RAGE expression at P56, but increased RAGE in the young adult PFC (P80). Adolescent intermittent ethanol exposure also increased TLR4 and HMGB1 expression at P56 that persisted into young adulthood (P80). Assessment of young adult frontal cortex mRNA (RT-PCR) found increased expression of proinflammatory cytokines, oxidases, and neuroimmune agonists at P80, 25days after ethanol treatment. Together, these human and animal data support the hypothesis that an early age of drinking onset upregulates RAGE/TLR4-HMGB1 and other neuroimmune genes that persist into young adulthood and could contribute to risk of alcoholism or other brain diseases associated with neuroinflammation. © 2013.

Latent Trajectories of Common Mental Health Disorder Risk Across 3 Decades of Adulthood in a Population-Based Cohort.

PubMed

Paksarian, Diana; Cui, Lihong; Angst, Jules; Ajdacic-Gross, Vladeta; Rössler, Wulf; Merikangas, Kathleen R

2016-10-01

Epidemiologic evidence indicates that most of the general population will experience a mental health disorder at some point in their lives. However, few prospective population-based studies have estimated trajectories of risk for mental disorders from young through middle adulthood to estimate the proportion of individuals who experience persistent mental disorder across this age period. To describe the proportion of the population who experience persistent mental disorder across adulthood and to estimate latent trajectories of disorder risk across this age period. A population-based, prospective cohort study was conducted between 1979 and 2008 in the canton of Zurich, Switzerland. A stratified random sample of 591 Swiss citizens was enrolled in 1978 at ages 19 years (men) and 20 years (women); 7 interviews were performed during a 29-year period. Men were sampled from military enrollment records and women from electoral records. From those initially enrolled, participants with high levels of psychiatric symptoms were oversampled for follow-up. Data analysis was performed from July 28, 2015, to June 8, 2016. Latent trajectories, estimated using growth mixture modeling, of past-year mood/anxiety disorder (ie, major depressive episode, phobias, panic, generalized anxiety disorder, and obsessive-compulsive disorder), substance use disorder (ie, drug abuse or dependence and alcohol abuse or dependence), and any mental disorder (ie, any of the above) assessed during in-person semistructured interviews at each wave. Diagnoses were based on DSM-III, DSM-III-R, and DSM-IV criteria. Of the 591 participants at baseline, 299 (50.6%) were female. Persistent mental health disorder across multiple study waves was rare. Among 252 individuals (42.6%) who participated in all 7 study waves, only 1.2% met criteria for disorder every time. Growth mixture modeling identified 3 classes of risk for any disorder across adulthood: low (estimated prevalence, 40.0%; 95% CI, -8.7% to 88.9%), increasing-decreasing (estimated prevalence, 15.3%; 95% CI, 1.0% to 29.6%), and increasing (estimated prevalence, 44.7%; 95% CI, -0.9% to 90.1%). Although no classes were characterized by persistently high disorder risk, for those in the increasing-decreasing class, risk was high from the late 20s to early 40s. Sex-specific models indicated 4 trajectory classes for women but only 3 for men. Persistently high mental health disorder risk across 3 decades of adulthood was rare in this population-based sample. Identifying early determinants of sex-specific risk trajectories would benefit prevention efforts.

Potential human exposures to neonicotinoid insecticides: A review.

PubMed

Zhang, Q; Li, Z; Chang, C H; Lou, J L; Zhao, M R; Lu, C

2018-05-01

Due to their systemic character and high efficacy to insect controls, neonicotinoid insecticides (neonics) have been widely used in global agriculture since its introduction in early 1990. Recent studies have indicated that neonics may be ubiquitous, have longer biological half-lives in the environment once applied, and therefore implicitly suggested the increasing probability for human exposure to neonics. Despite of neonics' persistent characters and widespread uses, scientific literature in regard of pathways in which human exposure could occur is relatively meager. In this review, we summarized results from peer-reviewed articles published prior to 2017 that address potential human exposures through ingestion and inhalation, as well as results from human biomonitoring studies. In addition, we proposed the use of relative potency factor approach in order to facilitate the assessment of concurrent exposure to a mixture of neonics with similar chemical structures and toxicological endpoints. We believe that the scientific information that we presented in this review will aid to future assessment of total neonic exposure and subsequently human health risk characterization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Temperature and population density determine reservoir regions of seasonal persistence in highland malaria.

PubMed

Siraj, Amir S; Bouma, Menno J; Santos-Vega, Mauricio; Yeshiwondim, Asnakew K; Rothman, Dale S; Yadeta, Damtew; Sutton, Paul C; Pascual, Mercedes

2015-12-07

A better understanding of malaria persistence in highly seasonal environments such as highlands and desert fringes requires identifying the factors behind the spatial reservoir of the pathogen in the low season. In these 'unstable' malaria regions, such reservoirs play a critical role by allowing persistence during the low transmission season and therefore, between seasonal outbreaks. In the highlands of East Africa, the most populated epidemic regions in Africa, temperature is expected to be intimately connected to where in space the disease is able to persist because of pronounced altitudinal gradients. Here, we explore other environmental and demographic factors that may contribute to malaria's highland reservoir. We use an extensive spatio-temporal dataset of confirmed monthly Plasmodium falciparum cases from 1995 to 2005 that finely resolves space in an Ethiopian highland. With a Bayesian approach for parameter estimation and a generalized linear mixed model that includes a spatially structured random effect, we demonstrate that population density is important to disease persistence during the low transmission season. This population effect is not accounted for in typical models for the transmission dynamics of the disease, but is consistent in part with a more complex functional form of the force of infection proposed by theory for vector-borne infections, only during the low season as we discuss. As malaria risk usually decreases in more urban environments with increased human densities, the opposite counterintuitive finding identifies novel control targets during the low transmission season in African highlands. © 2015 The Author(s).

Temperature and population density determine reservoir regions of seasonal persistence in highland malaria

PubMed Central

Siraj, Amir S.; Bouma, Menno J.; Santos-Vega, Mauricio; Yeshiwondim, Asnakew K.; Rothman, Dale S.; Yadeta, Damtew; Sutton, Paul C.; Pascual, Mercedes

2015-01-01

A better understanding of malaria persistence in highly seasonal environments such as highlands and desert fringes requires identifying the factors behind the spatial reservoir of the pathogen in the low season. In these ‘unstable’ malaria regions, such reservoirs play a critical role by allowing persistence during the low transmission season and therefore, between seasonal outbreaks. In the highlands of East Africa, the most populated epidemic regions in Africa, temperature is expected to be intimately connected to where in space the disease is able to persist because of pronounced altitudinal gradients. Here, we explore other environmental and demographic factors that may contribute to malaria's highland reservoir. We use an extensive spatio-temporal dataset of confirmed monthly Plasmodium falciparum cases from 1995 to 2005 that finely resolves space in an Ethiopian highland. With a Bayesian approach for parameter estimation and a generalized linear mixed model that includes a spatially structured random effect, we demonstrate that population density is important to disease persistence during the low transmission season. This population effect is not accounted for in typical models for the transmission dynamics of the disease, but is consistent in part with a more complex functional form of the force of infection proposed by theory for vector-borne infections, only during the low season as we discuss. As malaria risk usually decreases in more urban environments with increased human densities, the opposite counterintuitive finding identifies novel control targets during the low transmission season in African highlands. PMID:26631558

A longitudinal study of child sleep in high and low risk families: relationship to early maternal settling strategies and child psychological functioning.

PubMed

Sheridan, Andrew; Murray, Lynne; Cooper, Peter J; Evangeli, Michael; Byram, Victoria; Halligan, Sarah L

2013-03-01

To investigate whether sleep disturbances previously found to characterise high risk infants: (a) persist into childhood; (b) are influenced by early maternal settling strategies and (c) predict cognitive and emotional/behavioural functioning. Mothers experiencing high and low levels of psychosocial adversity (risk) were recruited antenatally and longitudinally assessed with their children. Mothers completed measures of settling strategies and infant sleep postnatally, and at 12 and 18 months, infant age. At five years, child sleep characteristics were measured via an actigraphy and maternal report; IQ and child adjustment were also assessed. Sleep disturbances observed in high-risk infants persisted at five years. Maternal involvement in infant settling was greater in high risk mothers, and predicted less optimal sleep at five years. Poorer five year sleep was associated with concurrent child anxiety/depression and aggression, but there was limited evidence for an influence of early sleep problems. Associations between infant/child sleep characteristics and IQ were also limited. Early maternal over-involvement in infant settling is associated with less optimal sleep in children, which in turn, is related to child adjustment. The findings highlight the importance of supporting parents in the early development of good settling practices, particularly in high-risk populations. Copyright © 2012 Elsevier B.V. All rights reserved.

Spatio-Temporal Dynamics of Asymptomatic Malaria: Bridging the Gap Between Annual Malaria Resurgences in a Sahelian Environment.

PubMed

Coulibaly, Drissa; Travassos, Mark A; Tolo, Youssouf; Laurens, Matthew B; Kone, Abdoulaye K; Traore, Karim; Sissoko, Mody; Niangaly, Amadou; Diarra, Issa; Daou, Modibo; Guindo, Boureima; Rebaudet, Stanislas; Kouriba, Bourema; Dessay, Nadine; Piarroux, Renaud; Plowe, Christopher V; Doumbo, Ogobara K; Thera, Mahamadou A; Gaudart, Jean

2017-12-01

In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009-2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2-3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009-2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

Differences in the Comparative Stability of Ebola Virus Makona-C05 and Yambuku-Mayinga in Blood

PubMed Central

Schuit, Michael; Miller, David M.; Reddick-Elick, Mary S.; Wlazlowski, Carly B.; Filone, Claire Marie; Herzog, Artemas; Colf, Leremy A.; Wahl-Jensen, Victoria; Hevey, Michael; Noah, James W.

2016-01-01

In support of the response to the 2013–2016 Ebola virus disease (EVD) outbreak in Western Africa, we investigated the persistence of Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 (EBOV/Mak-C05) on non-porous surfaces that are representative of hospitals, airplanes, and personal protective equipment. We performed persistence studies in three clinically-relevant human fluid matrices (blood, simulated vomit, and feces), and at environments representative of in-flight airline passenger cabins, environmentally-controlled hospital rooms, and open-air Ebola treatment centers in Western Africa. We also compared the surface stability of EBOV/Mak-C05 to that of the prototype Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Mayinga (EBOV/Yam-May), in a subset of these conditions. We show that on inert, non-porous surfaces, EBOV decay rates are matrix- and environment-dependent. Among the clinically-relevant matrices tested, EBOV persisted longest in dried human blood, had limited viability in dried simulated vomit, and did not persist in feces. EBOV/Mak-C05 and EBOV/Yam-May decay rates in dried matrices were not significantly different. However, during the drying process in human blood, EBOV/Yam-May showed significantly greater loss in viability than EBOV/Mak-C05 under environmental conditions relevant to the outbreak region, and to a lesser extent in conditions relevant to an environmentally-controlled hospital room. This factor may contribute to increased communicability of EBOV/Mak-C05 when surfaces contaminated with dried human blood are the vector and may partially explain the magnitude of the most recent outbreak, compared to prior outbreaks. These EBOV persistence data will improve public health efforts by informing risk assessments, structure remediation decisions, and response procedures for future EVD outbreaks. PMID:26849135

The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China.

PubMed

Loomis, Dana; Huang, Wei; Chen, Guosheng

2014-04-01

The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.

The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China

PubMed Central

Loomis, Dana; Huang, Wei; Chen, Guosheng

2014-01-01

The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population. PMID:24694836

High-Dose Azithromycin versus High-Dose Amoxicillin-Clavulanate for Treatment of Children with Recurrent or Persistent Acute Otitis Media

PubMed Central

Arrieta, Antonio; Arguedas, Adriano; Fernandez, Pilar; Block, Stan L.; Emperanza, Paz; Vargas, Sergio L.; Erhardt, William A.; de Caprariis, Pascal J.; Rothermel, Constance D.

2003-01-01

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged ≤2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged ≤2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged ≤2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM. PMID:14506028

Predictors of acute and persisting ischemic brain lesions in patients randomized to carotid stenting or endarterectomy.

PubMed

Rostamzadeh, Ayda; Zumbrunn, Thomas; Jongen, Lisa M; Nederkoorn, Paul J; Macdonald, Sumaira; Lyrer, Philippe A; Kappelle, L Jaap; Mali, Willem P Th M; Brown, Martin M; van der Worp, H Bart; Engelter, Stefan T; Bonati, Leo H

2014-02-01

We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study. We assessed acute lesions on diffusion-weighted imaging 1 to 3 days after treatment in 124 stenting and 107 endarterectomy patients and lesions persisting on fluid-attenuated inversion recovery after 1 month in 86 and 75 patients, respectively. Stenting patients had more acute (relative risk, 8.8; 95% confidence interval, 4.4-17.5; P<0.001) and persisting lesions (relative risk, 4.2; 95% confidence interval, 1.6-11.1; P=0.005) than endarterectomy patients. Acute lesion count was associated with age (by trend), male sex, and stroke as the qualifying event in stenting; high systolic blood pressure in endarterectomy; and white matter disease in both groups. The rate of conversion from acute to persisting lesions was lower in the stenting group (relative risk, 0.4; 95% confidence interval, 0.2-0.8; P=0.007), and was only predicted by acute lesion volume. Stenting caused more acute and persisting ischemic brain lesions than endarterectomy. However, the rate of conversion from acute to persisting lesions was lower in the stenting group, most likely attributable to lower acute lesion volumes. Clinical Trial Registration -URL: www.isrctn.org. Unique identifier: ISRCTN25337470.

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients.

PubMed

Osman, Marwan; Benamrouz, Sadia; Guyot, Karine; Baydoun, Martha; Frealle, Emilie; Chabe, Magali; Gantois, Nausicaa; Delaire, Baptiste; Goffard, Anne; Aoun, Albert; Jurdi, Nawaf; Dabboussi, Fouad; Even, Gael; Slomianny, Christian; Gosset, Pierre; Hamze, Monzer; Creusy, Colette; Viscogliosi, Eric; Certad, Gabriela

2017-01-01

The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients. Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65-9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44-89.02, P = 0.003). This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease.

Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

PubMed

Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

2016-03-01

Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research.

Immunobiology of HPV and HPV vaccines.

PubMed

Stanley, Margaret

2008-05-01

Genital human papillomavirus (HPV) infection with both low- and high-risk types is common, but most infections resolve as a result of a cell-mediated immune response. Failure to induce an effective immune response is related to inefficient activation of innate immunity and ineffective priming of the adaptive immune response; this defective immune response facilitates viral persistence, a key feature of high-risk HPV infection. This milieu becomes operationally HPV antigen tolerant, and the host's defenses become irrevocably compromised. HPV antigen-specific effector cells are poorly recruited to the infected focus and their activity is downregulated; neoplastic HPV containing cervical keratinocytes expressing high levels of E6 and E7 oncoproteins are not killed in this immunosuppressive, tolerant milieu, and progression to high-grade disease and cancer can result. Highly efficacious prophylactic HPV L1 virus-like particle (VLP) vaccines circumvent viral epithelial evasion strategies since they are delivered by intramuscular injection. The stromal dendritic cells of the muscle that encounter the highly immunogenic repeat structure of the VLP then migrate with their cargo to the lymph node, initiating an immune cascade that results in a robust T-cell dependent B-cell response, which generates high levels of L1-specific serum neutralizing antibodies and immune memory.

Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study.

PubMed

LaBeaud, A Desirée; Muiruri, Samuel; Sutherland, Laura J; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M; Peters, Clarence J; King, Charles H

2011-08-01

In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

PubMed Central

LaBeaud, A. Desirée; Muiruri, Samuel; Sutherland, Laura J.; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M.; Peters, Clarence J.; King, Charles H.

2011-01-01

Background In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006–2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. Methodology/Findings We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI95%:17%–29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI95%: 20%–39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT80)) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Conclusions Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at >1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks. PMID:21858236

Bioaccumulation and human health risk assessment of DDT and other organochlorine pesticides in an apex aquatic predator from a premier conservation area.

PubMed

Gerber, Ruan; Smit, Nico J; Van Vuren, Johan H J; Nakayama, Shouta M M; Yohannes, Yared B; Ikenaka, Yoshinori; Ishizuka, Mayumi; Wepener, Victor

2016-04-15

With the second highest gross domestic product in Africa, South Africa is known to have a high pesticide usage, including the highly persistent and banned group of organochlorine pesticides (OCPs). South Africa is also one of few countries to still actively spray DDT as malaria vector control. The aim of the study was to determine the degree to which aquatic biota in selected rivers of the world renowned Kruger National Park (KNP) are exposed to by use of OCPs in the catchments outside the KNP and how this exposure relates to human health. Tigerfish (Hydrocynus vittatus) are economically important apex predators and was selected as bioindicator for this study. Fish were sampled from the KNP sections of the Luvuvhu, Letaba and Olifants rivers during the high and low flow periods from 2010 to 2011 within the KNP and 19 OCPs were determined in muscle tissue using GC-ECD techniques. Significant flow related and spatial OCP bioaccumulation was observed. Tigerfish from the Luvuvhu River displayed the highest OCP bioaccumulation. Concentrations of the majority of the OCPs including the DDTs were the highest levels ever recorded from South African freshwater systems and in many cases the concentrations were higher than most contaminated areas from around the world. The concentrations found in H. vittatus muscle also exceeded maximum residue levels in edible fat as set by the European Union. The health risk assessment also demonstrated that the levels of OCPs pose very high cancer risks to the local populations consuming tigerfish, as high as 2 in 10 increased risk factor. This is of concern not only when managing the water resources of the conservation area but also for surrounding communities consuming freshwater fish. Contaminants enter the park from outside the borders and pose potential risks to the mandated conservation of aquatic biota within the KNP. Copyright © 2016 Elsevier B.V. All rights reserved.

HPV test by Hybrid Capture II for the diagnosis of HR-HPV persistent infection.

PubMed

Serour, Y; Bendahmane, M; Abbou Baker, F; Medles, M; Moueddene, B; Kraiba, R

2017-11-01

Persistent high-risk HPV (HR-HPV) infection is associated with a greater risk of cervical cancer. Statistical data on the prevalence of HR-HPV infections in the Algerian population is lacking. We conducted a prospective study of 300 women aged between 25 and 50 years, screened for cervical cancer from 2012 to 2015 in Sidi Bel Abbès, a western region of Algeria. We aimed to assess the reliability of the repeated use of the HC II test (three longitudinal HPV tests 9 months apart from each other) in diagnosing the persistence of HR-HPV infection. The prevalence of HR-HPV infection was 7.33% and infected women were aged 37.9±3years. For 90.9% of HR-HPV-positive patients, the infection persisted for a mean of 18.5months [95% CI: 16.9-22.1months]. Among these patients, 55.55% developed CIN1 and 11.11% developed CIN2. The sensitivity of the HC II test was 81.74% [95% CI: 71.3-89.6] and its positive predictive value associated with abnormal cervical biopsy was 27.49% [95% CI: 16.0-33.33]. Repeating the HC II test is a good predictor for identifying women at high risk of cervical cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Infectious Agents in Bovine Red Meat and Milk and Their Potential Role in Cancer and Other Chronic Diseases.

PubMed

Zur Hausen, Harald; Bund, Timo; de Villiers, Ethel-Michele

2017-01-01

Red meat and dairy products have frequently been suggested to represent risk factors for certain cancers, chronic neurodegenerative diseases, and autoimmune and cardiovascular disorders. This review summarizes the evidence and investigates the possible involvement of infectious factors in these diseases. The isolation of small circular single-stranded DNA molecules from serum and dairy products of Eurasian Aurochs (Bos taurus)-derived cattle, obviously persisting as episomes in infected cells, provides the basis for further investigations. Gene expression of these agents in human cells has been demonstrated, and frequent infection of humans is implicated by the detection of antibodies in a high percentage of healthy individuals. Epidemiological observations suggest their relationship to the development multiple sclerosis, to heterophile antibodies, and to N-glycolylneuraminic acid (Neu5Gc) containing cell surface receptors.

Will widespread human papillomavirus prophylactic vaccination change sexual practices of adolescent and young adult women in America?

PubMed

Monk, Bradley J; Wiley, Dorothy J

2006-08-01

Two virus-like particle human papillomavirus (HPV) vaccines have been shown to be nearly 100% effective in preventing type-specific persistent HPV infections and associated type-specific high-grade cervical intraepithelial neoplasia (CIN). Recently, it has been hypothesized that the administration of this vaccine to young girls in the United States might increase sexual promiscuity among adolescent women and/or young adults. Thus, it has been suggested that focused vaccine strategies either based on the risk of CIN or gender might be more rational or cost-effective. However, such strategies are unlikely to completely eradicate the burden of this disease and decrease the cost of cervical cancer screening. The suggestion that widespread vaccination will alter sexual practices is refuted and the rationale for the vaccination of all girls and boys is outlined.

The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced Carcinogenesis

PubMed Central

Olmedo-Nieva, Leslie; Muñoz-Bello, J. Omar; Contreras-Paredes, Adriana

2018-01-01

Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter. Through alternative splicing, this pre-mRNA produces a variety of E6 spliced transcripts termed E6*. In pre-malignant lesions and HPV-related cancers, different E6/E6* transcriptional patterns have been found, although they have not been clearly associated to cancer development. Moreover, there is a controversy about the participation of E6* proteins in cancer progression. This review addresses the regulation of E6 splicing and the different functions that have been found for E6* proteins, as well as their possible role in HPV-induced carcinogenesis. PMID:29346309

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

PubMed

Alberts, C J; Vos, R A; Borgdorff, H; Vermeulen, W; van Bergen, J; Bruisten, S M; Geerlings, S E; Snijder, M B; van Houdt, R; Morré, S A; de Vries, H J C; van de Wijgert, J H H M; Prins, M; Schim van der Loeff, M F

2016-12-01

In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

PubMed

Bazzano, L A; Hu, T; Bertisch, S M; Yao, L; Harville, E W; Gustat, J; Chen, W; Webber, L S; Shu, T; Redline, S

2016-12-01

Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). These results suggest that childhood OW is associated with a high risk of OSA in middle age. © 2016 World Obesity Federation.

Predicting persistent disabling low back pain in general practice: a prospective cohort study

PubMed Central

Jones, Gareth T; Johnson, Ruth E; Wiles, Nicola J; Chaddock, Carol; Potter, Richard G; Roberts, Chris; Symmons, Deborah PM; Macfarlane, Gary J

2006-01-01

Background Patients may adopt active and/or passive coping strategies in response to pain. However, it is not known whether these strategies may also precede the onset of chronic symptoms and, if so, whether they are independent predictors of prognosis. Aim To examine, in patients with low back pain in general practice, the prognostic value of active and passive coping styles, in the context of baseline levels of pain, disability and pain duration. Design of study Prospective cohort study. Setting Nine general practices in north west England. Method Patients consulting their GP with a new episode of low back pain were recruited to the study. Information on coping styles, pain severity, disability, duration, and a brief history of other chronic pain symptoms was recorded using a self-completion postal questionnaire. Participants were then sent a follow-up questionnaire, 3 months after their initial consultation, to assess the occurrence of low back pain. The primary outcome was persistent disabling low back pain, that is, low back pain at 3-month follow-up self-rated as ≥20 mm on a 100 mm visual analogue scale, and ≥5 on the Roland and Morris Disability Questionnaire. Results A total of 974 patients took part in the baseline survey, of whom 922 (95%) completed a follow-up questionnaire; 363 individuals (39%) reported persistent disabling pain at follow-up. Persons who reported high levels of passive coping experienced a threefold increase in the risk of persistent disabling low back pain (relative risk [RR] = 3.0; 95% confidence interval [CI] = 2.3 to 4.0). In contrast, active coping was associated with neither an increase nor a decrease in the risk of a poor prognosis. After adjusting for baseline pain severity, disability, and other measures of pain and pain history, persons who reported a high passive coping score were still at 50% increased risk of a poor outcome (RR = 1.5; 95% CI = 1.1 to 2.0). Conclusion Patients who report passive coping strategies experience a significant increase in the risk of persistent symptoms. Further, this risk persists after controlling for initial pain severity and disability. The identification of this low back pain subgroup may help target future treatments to those at greatest risk of a poor outcome. PMID:16638248

Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.

PubMed

Reinsmoen, Nancy L; Lai, Chi-Hung; Vo, Ashley; Jordan, Stanley C

2012-04-01

The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.

E. coli O157 on Scottish cattle farms: Evidence of local spread and persistence using repeat cross-sectional data

PubMed Central

2014-01-01

Background Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections. A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998 - 2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred. Results The presence of an E. coli O157 positive local farm (average distance: 5.96km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p < 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p < 0.001) from the same time frame. Conclusions The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources. PMID:24766709

Short- and medium-chain chlorinated paraffins in aquatic foods from 18 Chinese provinces: Occurrence, spatial distributions, and risk assessment.

PubMed

Wang, Runhua; Gao, Lirong; Zheng, Minghui; Tian, Yiling; Li, Jingguang; Zhang, Lei; Wu, Yongning; Huang, Huiting; Qiao, Lin; Liu, Wenbin; Su, Guijin; Liu, Guorui; Liu, Ying

2018-02-15

Short-chain chlorinated paraffins (SCCPs) are classed as persistent organic pollutants and were included in the Stockholm Convention in May 2017. Large amounts of chlorinated paraffins (CPs) are produced in China than in any other countries. CPs can be released into the environment while being produced and used, and can bioaccumulate in aquatic biota and be ingested by humans. Dietary intake is the main route through which humans are exposed to CPs. It has previously been found that persistent organic pollutant concentrations are usually higher in aquatic foods than in other foods. The risk of human exposure to SCCPs in aquatic foods should therefore be of concerns. However, SCCP concentrations in aquatic foods have not been systematically studied. A total of 1620 aquatic food samples were collected, and 18 pooled samples were analyzed by two-dimensional gas chromatography coupled with electron-capture negative-ionization time-of-flight mass spectrometry. The mean SCCP and MCCP concentrations were 1472 and 80.5ng/gwet weight, respectively. The dominant SCCP and MCCP congener groups were C 10 Cl 6-7 and C 14 Cl 7-8 , respectively. The concentrations were much higher than those have been found in aquatic foods in other countries. The CP concentrations in the samples consumed by local people from eastern and southern China were higher than the concentrations in samples from central and western China. Risk assessment results indicated that SCCPs and MCCPs in aquatic foods do not pose significant risks to residents of China. Copyright © 2017 Elsevier B.V. All rights reserved.

Differentiating early-onset persistent versus childhood-limited conduct problem youth.

PubMed

Barker, Edward D; Maughan, Barbara

2009-08-01

Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

PubMed

Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

2014-01-01

The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Reducing persistent polyomavirus infection increases functionality of virus-specific memory CD8 T cells.

PubMed

Qin, Qingsong; Lauver, Matthew; Maru, Saumya; Lin, Eugene; Lukacher, Aron E

2017-02-01

Mouse polyomavirus (MuPyV) causes a smoldering persistent infection in immunocompetent mice. To lower MuPyV infection in acutely and persistently infected mice, and study the impact of a temporal reduction in viral loads on the memory CD8 T cell response, we created a recombinant MuPyV in which a loxP sequence was inserted into the A2 strain genome upstream of the early promoter and another loxP sequence was inserted in cis into the intron shared by all three T antigens. Using mice transgenic for tamoxifen-inducible Cre recombinase, we demonstrated that reduction in MuPyV load during persistent infection was associated with differentiation of virus-specific CD8 T cells having a superior recall response. Evidence presented here supports the concept that reduction in viral load during persistent infection can promote differentiation of protective virus-specific memory CD8 T cells in patients at risk for diseases caused by human polyomaviruses. Copyright © 2016 Elsevier Inc. All rights reserved.

Pregnancy persistently affects memory T cell populations.

PubMed

Kieffer, Tom E C; Faas, Marijke M; Scherjon, Sicco A; Prins, Jelmer R

2017-02-01

Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the constitution, size and activation status of peripheral human memory T-lymphocyte populations. Effector memory (EM) and central memory (CM) T-lymphocytes were analyzed using flow cytometry of peripheral blood from 14 nulligravid, 12 primigravid and 15 parous women that were on average 18 months postpartum. The short term effects were shown by the significantly higher CD4+ EM cell and activated CD4+ memory cell proportions in primigravid women compared to nulligravid women. The persistent effects found in this study were the significantly higher proportions of CD4+ EM, CD4+ CM and activated memory T cells in parous women compared to nulligravid women. In contrast to CD4+ cells, activation status of CD8+ memory cells did not differ between the groups. This study shows that pregnancy persistently affects the pre-pregnancy CD4+ memory cell pool in human peripheral blood. During pregnancy, CD4+ T-lymphocytes might differentiate into EM cells followed by persistent higher proportions of CD4+ CM and EM cells postpartum. The persistent effects of pregnancy on memory T cells found in this study support the hypothesis that memory T cells are generated during pregnancy and that these cells could be involved in the lower complication risks in multiparous pregnancies in humans. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Increased Mortality Risk in Older Adults with Persistently Low or Declining Feelings of Usefulness to Others

PubMed Central

Gruenewald, Tara L.; Karlamangla, Arun S.; Greendale, Gail A.; Singer, Burton H.; Seeman, Teresa E.

2009-01-01

Objectives To determine if persistently low or declining feelings of usefulness to others in later life predicts increased mortality hazard in older adults. Methods Data on change in perceptions of usefulness, health, behavioral and psychosocial covariate factors, and mortality originate from the MacArthur Study of Successful Aging, a prospective study of 1,189 older adults (age 70–79 years). Results Older adults with persistently low feelings of usefulness or who experienced a decline to low feelings of usefulness over the first 3-years of the study experienced a greater hazard of mortality (sociodemographic adjusted HR = 1.75 (95% CI = 1.22 to 2.51)) over a subsequent 9-year follow-up as compared to older adults with persistently high feelings of usefulness. Discussion Older adults with persistently low perceived usefulness or feelings of usefulness that decline to a low level may be a vulnerable group with increased risk for poor health outcomes in later life. PMID:19104034

APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

PubMed Central

Cooper, Anneli; Ilboudo, Hamidou; Alibu, V Pius; Ravel, Sophie; Enyaru, John; Weir, William; Noyes, Harry; Capewell, Paul; Camara, Mamadou; Milet, Jacqueline; Jamonneau, Vincent; Camara, Oumou; Matovu, Enock; Bucheton, Bruno; MacLeod, Annette

2017-01-01

Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney disease risk, named G1 and G2, occur at high frequency. APOL1 is a trypanolytic protein that confers innate resistance to most African trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human African trypanosomiasis. In this case-control study, we test the prevailing hypothesis that these APOL1 variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against T.b. rhodesiense infection. Furthermore, we report unpredicted strong opposing associations with T.b. gambiense disease outcome. G2 associates with faster progression of T.b. gambiense trypanosomiasis, while G1 associates with asymptomatic carriage and undetectable parasitemia. These results implicate both forms of human African trypanosomiasis in the selection and persistence of otherwise detrimental APOL1 kidney disease variants. DOI: http://dx.doi.org/10.7554/eLife.25461.001 PMID:28537557

No Evidence of Presence of Parvovirus 4 in a Swedish Cohort of Severely Immunocompromised Children and Adults

PubMed Central

Tolfvenstam, Thomas; Norbeck, Oscar; Öhrmalm, Lars

2012-01-01

The recently discovered human parvovirus 4 (PARV4) has been associated with seropositivity for human immunodeficiency virus, hepatitis B virus and hepatitis C virus. High prevalence is seen especially in intravenous drug users. The virus has been detected in blood products and persons who have been repeatedly transfused have shown to be a risk-group. Furthermore, reports from different parts of the world suggesting a prevalence ranging from zero to one third of the healthy population and the virus is thought to cause a latent or persistent infection. We investigated the presence of PARV4 DNA and parvovirus B19 (B19) DNA in serum from 231 severely immunocompromised cancer patients that have been exposed for blood products. Compared to B19, which was found in 3.9% of the patients, we found no evidence of PARV4. Our results may indicate a very low prevalence of the virus in Sweden, and it would be useful to measure the real PARV4 exposure of the healthy population as well as individuals with known risk factors by serology. PMID:23050026

When environmentally persistent pathogens transform good habitat into ecological traps.

PubMed

Leach, Clinton B; Webb, Colleen T; Cross, Paul C

2016-03-01

Habitat quality plays an important role in the dynamics and stability of wildlife metapopulations. However, the benefits of high-quality habitat may be modulated by the presence of an environmentally persistent pathogen. In some cases, the presence of environmental pathogen reservoirs on high-quality habitat may lead to the creation of ecological traps, wherein host individuals preferentially colonize high-quality habitat, but are then exposed to increased infection risk and disease-induced mortality. We explored this possibility through the development of a stochastic patch occupancy model, where we varied the pathogen's virulence, transmission rate and environmental persistence as well as the distribution of habitat quality in the host metapopulation. This model suggests that for pathogens with intermediate levels of spread, high-quality habitat can serve as an ecological trap, and can be detrimental to host persistence relative to low-quality habitat. This inversion of the relative roles of high- and low-quality habitat highlights the importance of considering the interaction between spatial structure and pathogen transmission when managing wildlife populations exposed to an environmentally persistent pathogen.

When environmentally persistent pathogens transform good habitat into ecological traps

USGS Publications Warehouse

Leach, Clint; Webb, Colleen T.; Cross, Paul C.

2016-01-01

Habitat quality plays an important role in the dynamics and stability of wildlife metapopulations. However, the benefits of high-quality habitat may be modulated by the presence of an environmentally persistent pathogen. In some cases, the presence of environmental pathogen reservoirs on high-quality habitat may lead to the creation of ecological traps, wherein host individuals preferentially colonize high-quality habitat, but are then exposed to increased infection risk and disease-induced mortality. We explored this possibility through the development of a stochastic patch occupancy model, where we varied the pathogen’s virulence, transmission rate and environmental persistence as well as the distribution of habitat quality in the host metapopulation. This model suggests that for pathogens with intermediate levels of spread, high-quality habitat can serve as an ecological trap, and can be detrimental to host persistence relative to low-quality habitat. This inversion of the relative roles of high- and low-quality habitat highlights the importance of considering the interaction between spatial structure and pathogen transmission when managing wildlife populations exposed to an environmentally persistent pathogen.

ONE FISH, TWO FISH, RED FISH, BLUE FISH: THE FISH QUALITY INDEX AS A RISK COMMUNICATION TOOL

EPA Science Inventory

Many people are at high risk for methyl mercury toxicity because of their consumption of contaminated fish. Often health risks of Persistent Bioaccumulative Toxicants (PT) such as methyl mercury, PCBs or Dioxins are underestimated because of their amplification in the food chain ...

Timing and Duration of Traffic-related Air Pollution Exposure and the Risk for Childhood Wheeze and Asthma.

PubMed

Brunst, Kelly J; Ryan, Patrick H; Brokamp, Cole; Bernstein, David; Reponen, Tiina; Lockey, James; Khurana Hershey, Gurjit K; Levin, Linda; Grinshpun, Sergey A; LeMasters, Grace

2015-08-15

The timing and duration of traffic-related air pollution (TRAP) exposure may be important for childhood wheezing and asthma development. We examined the relationship between TRAP exposure and longitudinal wheezing phenotypes and asthma at age 7 years. Children completed clinical examinations annually from age 1 year through age 4 years and age 7 years. Parental-reported wheezing was assessed at each age, and longitudinal wheezing phenotypes (early-transient, late-onset, persistent) and asthma were defined at age 7 years. Participants' time-weighted exposure to TRAP, from birth through age 7 years, was estimated using a land-use regression model. The relationship between TRAP exposure and wheezing phenotypes and asthma was examined. High TRAP exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] = 1.64; 95% confidence interval [CI], 1.04-2.57 and aOR = 2.31; 95% CI, 1.28-4.15, respectively); exposure from birth to age 1 year and age 1 to 2 years was also associated with persistent wheeze. Only children with high average TRAP exposure from birth through age 7 years were at significantly increased risk for asthma (aOR = 1.71; 95% CI, 1.01-2.88). Early-life exposure to TRAP is associated with increased risk for persistent wheezing, but only long-term exposure to high levels of TRAP throughout childhood was associated with asthma development.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

78 FR 42963 - Assessment of the Risk of Human Salmonellosis Associated With the Consumption of Tree Nuts...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-18

...., pre- processing storage conditions, processing treatments and conditions, post-processing storage, etc... outbreak strain was shown to persist in one of the affected orchards for a period of at least 5 years... before, during, and after application of treatments designed to reduce bacterial contamination), retail...

Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease (COPD) in a non-human primate model of AIDS

PubMed Central

Shipley, Timothy W.; Kling, Heather M.; Morris, Alison; Patil, Sangita; Kristoff, Jan; Guyach, Siobhan E.; Murphy, Jessica M.; Shao, Xiuping; Sciurba, Frank C.; Rogers, Robert M.; Richards, Thomas; Thompson, Paul; Montelaro, Ronald C.; Coxson, Harvey O.; Hogg, James C.; Norris, Karen A.

2010-01-01

HIV-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with sub-clinical infection has been postulated to promote COPD. Persistence of Pneumocystis (Pc) is associated with HIV and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus (SHIV) model of HIV infection to study pulmonary effects of Pc colonization. SHIV-infected/Pc-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Elevated Th2 cytokines and pro-inflammatory mediators in bronchoalveolar lavage fluid coincided with Pc colonization and pulmonary function decline. These results support the concept that an infectious agent contributes to development of HIV-associated lung disease and suggests that Pc colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression thus identifying potential therapeutic targets for COPD. PMID:20533880

Assessment of Chlamydia psittaci Shedding and Environmental Contamination as Potential Sources of Worker Exposure throughout the Mule Duck Breeding Process

PubMed Central

Hulin, V.; Bernard, P.; Vorimore, F.; Aaziz, R.; Cléva, D.; Robineau, J.; Durand, B.; Angelis, L.

2015-01-01

Chlamydia psittaci is an obligate intracellular bacterium responsible for avian chlamydiosis, otherwise known as psittacosis, a zoonotic disease that may lead to severe atypical pneumonia. This study was conducted on seven mule duck flocks harboring asymptomatic birds to explore the circulation and persistence of C. psittaci during the entire breeding process and assess the potential sources of worker exposure. Cloacal swabs and air samples were taken on each occasion requiring humans to handle the birds. In parallel, environmental samples, including dust, water, and soil, were collected. Specific real-time PCR analyses revealed the presence of C. psittaci in all flocks but with three different shedding patterns involving ducks about the age of 4, 8, and 12 weeks with heavy, moderate, and low excretion levels, respectively. Air samples were only positive in flocks harboring heavy shedders. Dust in flocks with heavy or moderate shedders carried chlamydial loads strongly associated with the loads detected in avian and soil samples. Environmental contamination, significantly correlated with shedding dynamics, was considered to be the most probable source of exposure. The high prevalence of bacteriophage Chp1 in all flocks, mostly jointly present with chlamydia, suggests an important factor in C. psittaci persistence, thus creating a greater risk for humans. A survey conducted in these flocks regarding farming practices and activities showed that disinfection seems to be the most promising practice for reducing C. psittaci prevalence in ducks and that the place and the duration of action during operations seem to be potential risk factors. Strict adherence to good practices is strongly recommended. PMID:26712548

Can demographic, clinical and treatment-related factors available at hormonal therapy initiation predict non-persistence in women with stage I-III breast cancer?

PubMed

Cahir, Caitriona; Barron, Thomas I; Sharp, Linda; Bennett, Kathleen

2017-03-01

To investigate whether demographic, clinical and treatment-related risk factors known at treatment initiation can be used to reliably predict future hormonal therapy non-persistence in women with breast cancer, and to inform intervention development. Women with stage I-III breast cancer diagnosed 2000-2012 and prescribed hormonal therapy were identified from the National Cancer Registry Ireland (NCRI) and linked to pharmacy claims data from Ireland's Primary Care Reimbursement Services (PCRS). Non-persistence was defined as a treatment gap of ≥180 days within 5 years of initiation. Seventeen demographic, clinical and treatment-related risk factors, identified from a systematic review, were abstracted from the NCRI-PCRS dataset. Multivariate binomial models were used to estimate relative risks (RR) and risk differences (RD) for associations between risk factors and non-persistence. Calibration and discriminative performance of the models were assessed. The analysis was repeated for early non-persistence (<1 year of initiation). Within 5 years of treatment initiation 680 women (19.9%) were non-persistent. Women aged <50 years (adjusted RR 1.41, 95% CI 1.16-1.70) and those prescribed antidepressants (RR 1.22, 95% CI 1.04-1.45) had increased risk of non-persistence. Married women (RR 0.82 95% CI 0.71-0.94) and those with prior medication use (RR 0.62 95% CI 0.51-0.75) had reduced risk of non-persistence. The area under the receiver-operating characteristic (ROC) curve for non-persistence was 0.61. Findings were similar for early non-persistence. The risk prediction model did not discriminate well between women at higher and lower risk of non-persistence at treatment initiation. Future studies should consider other factors, such as psychological characteristics and experience of side-effects.

Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study.

PubMed

Kanchanomai, Siriluck; Janwantanakul, Prawit; Pensri, Praneet; Jiamjarasrangsi, Wiroj

2011-07-15

Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life. A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain. Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies. Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic.

Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study

PubMed Central

2011-01-01

Background Although neck pain is common in young adulthood, studies on predictive factors for its onset and persistence are scarce. It is therefore important to identify possible risk factors among young adults so as to prevent the development of neck pain later in life. Methods A prospective study was carried out in healthy undergraduate students. At baseline, a self-administered questionnaire and standardized physical examination were used to collect data on biopsychosocial factors. At 3, 6, 9, and 12 months thereafter, follow-up data were collected on the incidence of neck pain. Those who reported neck pain on ≥ 2 consecutive follow-ups were categorized as having persistent neck pain. Two regression models were built to analyze risk factors for the onset and persistence of neck pain. Results Among the recruited sample of 684 students, 46% reported the onset of neck pain between baseline and 1-year follow-up, of whom 33% reported persistent neck pain. The onset of neck pain was associated with computer screen position not being level with the eyes and mouse position being self-rated as suitable. Factors that predicted persistence of neck pain were position of the keyboard being too high, use of computer for entertainment < 70% of total computer usage time, and students being in the second year of their studies. Conclusion Neck pain is quite common among undergraduate students. This study found very few proposed risk factors that predicted onset and persistence of neck pain. The future health of undergraduate students deserves consideration. However, there is still much uncertainty about factors leading to neck pain and more research is needed on this topic. PMID:21756362

Genital warts in children: what do they mean?

PubMed Central

Jayasinghe, Y; Garland, S M

2006-01-01

Human papillomaviruses (HPVs) are a diverse family of viruses, of which 30–40 genotypes specifically infect the genital tract. Genital HPVs are largely transmitted sexually, with most infections being asymptomatic and transient. In contrast, persistent infection with oncogenic genotypes in a minority is a strong risk factor, for subsequent development of high grade dysplasia, the precursor lesion to cervical neoplasia, which generally occurs after a long latency period. It is unknown whether there is a disease correlate in children chronically infected with oncogenic HPVs. Low risk HPV genotypes 6 and 11 are the primary cause of condylomata acuminata, although in children non‐genital genotypes are also found in a proportion, with the mode of transmission being either perinatal, horizontal, or sexual. The finding of asymptomatic HPV DNA in children, and correlation with live virus, infectivity, or disease is unclear. Long term follow up for children with anogenital warts is recommended, although there are no longitudinal studies available to clarify whether they are at risk of developing carcinoma in young adulthood. PMID:16670117

Impact of Vaccination on 14 High-Risk HPV Type Infections: A Mathematical Modelling Approach

PubMed Central

Vänskä, Simopekka; Auranen, Kari; Leino, Tuija; Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Tiihonen, Petri; Apter, Dan; Lehtinen, Matti

2013-01-01

The development of high-risk human papillomavirus (hrHPV) infection to cervical cancer is a complicated process. We considered solely hrHPV infections, thus avoiding the confounding effects of disease progression, screening, and treatments. To analyse hrHPV epidemiology and to estimate the overall impact of vaccination against infections with hrHPVs, we developed a dynamic compartmental transmission model for single and multiple infections with 14 hrHPV types. The infection-related parameters were estimated using population-based sexual behaviour and hrHPV prevalence data from Finland. The analysis disclosed the important role of persistent infections in hrHPV epidemiology, provided further evidence for a significant natural immunity, and demonstrated the dependence of transmission probability estimates on the model structure. The model predicted that vaccinating girls at 80% coverage will result in a 55% reduction in the overall hrHPV prevalence and a higher 65% reduction in the prevalence of persistent hrHPV infections in females. In males, the reduction will be 42% in the hrHPV prevalence solely by the herd effect from the 80% coverage in girls. If such high coverage among girls is not reached, it is still possible to reduce the female hrHPV prevalence indirectly by the herd effect if also boys are included in the vaccination program. On the other hand, any herd effects in older unvaccinated cohorts were minor. Limiting the epidemiological model to infection yielded improved understanding of the hrHPV epidemiology and of mechanisms with which vaccination impacts on hrHPV infections. PMID:24009669

Human in Vivo pharmacokinetics of [ 14C]Dibenzo[ def,p]chrysene by accelerator mass spectrometry following oral microdosing

DOE PAGES

Madeen, Erin; Corley, Richard A.; Crowell, Susan; ...

2014-11-24

Dibenzo( def,p)chrysene (DBC), (also known as dibenzo[a,l]pyrene), is a high molecular weight polycyclic aromatic hydrocarbon (PAH) found in the environment, including food, produced by the incomplete combustion of hydrocarbons. DBC, classified by IARC as a 2A probable human carcinogen, has a relative potency factor (RPF) in animal cancer models 30-fold higher than benzo[ a]pyrene. No data are available describing the disposition of high molecular weight (>4 rings) PAHs in humans to compare to animal studies. Pharmacokinetics of DBC was determined in 3 female and 6 male human volunteers following oral microdosing (29 ng, 5 nCi) of [ 14C]-DBC. This studymore » was made possible with highly sensitive accelerator mass spectrometry (AMS), capable of detecting [ 14C]-DBC equivalents in plasma and urine following a dose considered of de minimus risk to human health. Plasma and urine were collected over 72 h. The plasma C max was 68.8 ± 44.3 fg·mL –1 with a T max of 2.25 ± 1.04 h. Elimination occurred in two distinct phases: a rapid (α)-phase, with a T 1/2 of 5.8 ± 3.4 h and an apparent elimination rate constant (K el) of 0.17 ± 0.12 fg·h –1, followed by a slower (β)-phase, with a T 1/2 of 41.3 ± 29.8 h and an apparent K el of 0.03 ± 0.02 fg·h –1. In spite of the high degree of hydrophobicity (log Kow of 7.4), DBC was eliminated rapidly in humans, as are most PAHs in animals, compared to other hydrophobic persistent organic pollutants such as, DDT, PCBs and TCDD. Preliminary examination utilizing a new UHPLC-AMS interface, suggests the presence of polar metabolites in plasma as early as 45 min following dosing. Finally, this is the first in vivo data set describing pharmacokinetics in humans of a high molecular weight PAH and should be a valuable addition to risk assessment paradigms.« less

Human in Vivo pharmacokinetics of [ 14C]Dibenzo[ def,p]chrysene by accelerator mass spectrometry following oral microdosing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madeen, Erin; Corley, Richard A.; Crowell, Susan

Dibenzo( def,p)chrysene (DBC), (also known as dibenzo[a,l]pyrene), is a high molecular weight polycyclic aromatic hydrocarbon (PAH) found in the environment, including food, produced by the incomplete combustion of hydrocarbons. DBC, classified by IARC as a 2A probable human carcinogen, has a relative potency factor (RPF) in animal cancer models 30-fold higher than benzo[ a]pyrene. No data are available describing the disposition of high molecular weight (>4 rings) PAHs in humans to compare to animal studies. Pharmacokinetics of DBC was determined in 3 female and 6 male human volunteers following oral microdosing (29 ng, 5 nCi) of [ 14C]-DBC. This studymore » was made possible with highly sensitive accelerator mass spectrometry (AMS), capable of detecting [ 14C]-DBC equivalents in plasma and urine following a dose considered of de minimus risk to human health. Plasma and urine were collected over 72 h. The plasma C max was 68.8 ± 44.3 fg·mL –1 with a T max of 2.25 ± 1.04 h. Elimination occurred in two distinct phases: a rapid (α)-phase, with a T 1/2 of 5.8 ± 3.4 h and an apparent elimination rate constant (K el) of 0.17 ± 0.12 fg·h –1, followed by a slower (β)-phase, with a T 1/2 of 41.3 ± 29.8 h and an apparent K el of 0.03 ± 0.02 fg·h –1. In spite of the high degree of hydrophobicity (log Kow of 7.4), DBC was eliminated rapidly in humans, as are most PAHs in animals, compared to other hydrophobic persistent organic pollutants such as, DDT, PCBs and TCDD. Preliminary examination utilizing a new UHPLC-AMS interface, suggests the presence of polar metabolites in plasma as early as 45 min following dosing. Finally, this is the first in vivo data set describing pharmacokinetics in humans of a high molecular weight PAH and should be a valuable addition to risk assessment paradigms.« less

Identification of new metabolic pathways in the enantioselective fungicide tebuconazole biodegradation by Bacillus sp. 3B6.

PubMed

Youness, Mohamed; Sancelme, Martine; Combourieu, Bruno; Besse-Hoggan, Pascale

2018-06-05

The use of triazole fungicides in various fields ranging from agriculture to therapy, can cause long-term undesirable effects on different organisms from various environmental compartments and lead to resistance phenomena (even in humans) due to their extensive use and persistence. Their occurrence in various water bodies has increased and tebuconazole, in particular, is often detected, sometimes in high concentration. Only a few bacterial and fungal strains have been isolated and found to biotransform this fungicide, described as not easily biodegradable. Nevertheless, the knowledge of efficient degrading-strains and metabolites potentially formed could improve bioremediation process and global overview of risk assessment. Therefore, a broad screening of microorganisms, isolated from various environmental compartments or from commercially-available strain collections, allowed us to find six bacterial strains able to biotransform tebuconazole. The most efficient one was studied further: this environmental strain Bacillus sp. 3B6 biotransforms the fungicide enantioselectively (ee = 18%) into two hydroxylated metabolites, one of them being transformed in its turn to alkene by a biotic dehydration reaction. This original enantioselective pathway shows that racemic pesticides should be treated by the environmental risk assessment authorities as a mixture of two compounds because persistence, biodegradation, bioaccumulation and toxicity often show chiral dependence. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of pain catastrophizing with the incidence and severity of acute and persistent perineal pain after natural childbirth: longitudinal cohort study.

PubMed

Soares, Anne Danielle Santos; Couceiro, Tânia Cursino de Menezes; Lima, Luciana Cavalcanti; Flores, Fernanda Lobo Lago; Alcoforado, Eusa Maria Belarmino; Filho, Roberto de Oliveira Couceiro

2013-01-01

Vaginal birth delivery may result in acute and persistent perineal pain postpartum. This study evaluated the association between catastrophizing, a phenomenon of poor psychological adjustment to pain leading the individual to magnify the painful experience making it more intense, and the incidence and severity of perineal pain and its relationship to perineal trauma. Cohort study conducted with pregnant women in labor. We used the pain catastrophizing scale during hospitalization and assessed the degree of perineal lesion and pain severity in the first 24 hours and after 8 weeks of delivery using a numerical pain scale. We evaluated 55 women, with acute pain reported by 69.1%, moderate/severe pain by 36.3%, and persistent pain by 14.5%. Catastrophizing mean score was 2.15 ± 1.24. Catastrophizing patients showed a 2.90 relative risk (RR) for perineal pain (95% CI: 1.08-7.75) and RR: 1.31 for developing persistent perineal pain (95% CI: 1.05-1.64). They also showed a RR: 2.2 for developing acute and severe perineal pain (95% CI: 1.11-4.33). The incidence of acute and persistent perineal pain after vaginal delivery is high. Catastrophizing pregnant women are at increased risk for developing acute and persistent perineal pain, as well as severe pain. Perineal trauma increased the risk of persistent perineal pain. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[HPV immunization for the prevention of cervical cancer].

PubMed

Mougin, Christiane; Bourgault-Villada, Isabelle; Coursaget, Pierre

2009-12-01

Human Papillomaviruses (HPV) infect epithelial cells of the skin and mucosae. Mucosal high-risk HPV types (mainly HPV 16 and 18) are involved in the development of cervical cancer, one of the most common cancers in young women. HPV infection is usually asymptomatic and clears spontaneously, but 10 - 15 % of high-risk HPV infections are persistent and increase the risk of precancerous and cancerous lesions of the cervix. Two HPV vaccines have been licensed to provide protection against cervical cancer. To report the different aspects of HPV infection in order to improve the understanding of the particular problems of HPV vaccination and to review the most recent findings related to HPV vaccines, particularly regarding the protective efficacy of vaccines and the roles of adjuvants and immune response in protection. Articles were selected from the PubMed database (National Library of Medicine- National Institute of Health) with the following Keywords "HPV", "Prevention", "HPV vaccines", "Immune response", "Antibody". Abstracts of oral presentations from international meetings were also selected for the more recent findings. a critical analysis of the majority of papers published was undertaken and relevant information summarized. Virus-like particle production by expressing the major protein of the HPV capsid was carried out in the early 90's, leading to the recent development of two HPV vaccines. These vaccines are now licensed in many countries and have been demonstrated to be highly immunogenic. In subjects that are non-infected at the time of vaccination, HPV vaccines are highly effective in preventing persistent HPV 16 - 18 infections (90 %) and precursors lesions of cervical cancer associated with these two HPV types (close to 100 %). Clinical trials have also confirmed that HPV vaccines are well tolerated by recipients. The present paper is a detailed review published in French on HPV vaccines, their efficacy in the prevention of HPV infections and unresolved questions regarding the use of HPV vaccines. This report also includes biological and immunological information to improve the understanding of HPV vaccination.

A General Model of Dioxin Contamination in Breast Milk: Results from a Study on 94 Women from the Caserta and Naples Areas in Italy

PubMed Central

Rivezzi, Gaetano; Piscitelli, Prisco; Scortichini, Giampiero; Giovannini, Armando; Diletti, Gianfranco; Migliorati, Giacomo; Ceci, Roberta; Rivezzi, Giulia; Cirasino, Lorenzo; Carideo, Pietro; Black, Dennis M.; Garzillo, Carmine; Giani, Umberto

2013-01-01

Background: The Caserta and Naples areas in Campania Region experience heavy environmental contamination due to illegal waste disposal and burns, thus representing a valuable setting to develop a general model of human contamination with dioxins (PCDDs-PCDFs) and dioxin-like-PCBs (dl-PCBs). Methods: 94 breastfeeding women (aged 19–32 years; mean age 27.9 ± 3.0) were recruited to determine concentrations of PCDDs-PCDFs and dl-PCBs in their milk. Individual milk samples were collected and analyzed according to standard international procedures. A generalized linear model was used to test potential predictors of pollutant concentration in breast milk: age, exposure to waste fires, cigarette smoking, diet, and residence in high/low risk area (defined at high/low environmental pressure by a specific 2007 WHO report). A Structural Equation Model (SEM) analysis was carried out by taking into account PCDDs-PCDFs and dl-PCBs as endogenous variables and age, waste fires, risk area and smoking as exogenous variables. Results: All milk samples were contaminated by PCDDs-PCDFs (8.6 pg WHO-TEQ/98g fat ± 2.7; range 3.8–19) and dl-PCBs (8.0 pg WHO-TEQ/98g fat ± 3.7; range 2.5–24), with their concentrations being associated with age and exposure to waste fires (p < 0.01). Exposure to fires resulted in larger increases of dioxins concentrations in people living in low risk areas than those from high risk areas (p < 0.01). Conclusions: A diffuse human exposure to persistent organic pollutants was observed in the Caserta and Naples areas. Dioxins concentration in women living in areas classified at low environmental pressure in 2007 WHO report was significantly influenced by exposure to burns. PMID:24217180

Prevalence and Persistence of Cervical Human Papillomavirus Infection In HIV-Positive Women Initiating Highly-Active Antiretroviral Therapy

PubMed Central

Fife, Kenneth H.; Wu, Julia W.; Squires, Kathleen E.; Watts, D. Heather; Andersen, Janet W.; Brown, Darron R.

2009-01-01

Objective To determine the prevalence of HPV DNA in cervical specimens from treatment-naïve women initiating highly active antiretroviral therapy (HAART) and explore the longitudinal association of HPV DNA with CD4 count and HIV viral load (VL). Methods Women enrolled prior to HAART were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical swab for HPV DNA. Results The 146 subjects had a median CD4 count of 238 cells/μL and VL of 13,894 copies/mL. Ninety-seven (66%) subjects had HPV DNA detected in the baseline specimen including 90 subjects (62%) positive for one or more high risk HPV types. HPV DNA detection declined to 49% at week 96, and that of a high risk HPV type to 39%. The duration of follow-up was associated with decreased detection of HPV DNA of any type (p=0.045) and of high risk HPV types (p=0.003). There was at most a marginal association between HAART response and loss of detection of cervical HPV DNA. Conclusions Women initiating HAART had a high prevalence of cervical HPV DNA that declined over 96 weeks of HAART. The relationship of CD4 count and VL response to the decline of cervical HPV DNA was not strong. PMID:19387354

Fate and transport of some selected PhACs in a river receiving a high load of treated sewage

NASA Astrophysics Data System (ADS)

Bendz, D.; Ginn, T. R.; Paxeus, N.

2003-04-01

Pharmaceutical active compounds (PhACs) have lately been acknowledged to constitute a risk for humans and for the terrestrial and aquatic environment. Human and veterinary applications are the main sources of PhACs in the environment and the major pathway are excretion and discharge to the environment. Sewage treatment plants (STPs) play a crucial role for the introduction of the human PhACs in the environment through its removal efficiency and by separating these compounds into two exposure pathways associated with the aquatic and the solid (sludge) phase, respectively. Actually, STPs are recognized as being the main point discharge sources of human PhACs to the aquatic environment. In this study the fate and transport of a selected human PhACs belonging to different therapeutic classes (NSAIDs- non-steroidal antiinflamatory drugs, lipid regulators, antiepileptics, antibiotics and &beta-blockers) are investigated in a small river in the very south of Sweden receiving a high load of treated wastewater. In addition to the PhACs, triclosan (commonly used biocide) was included in this study. Water samples were taken of incoming and outgoing wastewater from the treatment plant, at the effluent in the river, and along the river up to 8 kilometers downstream were the river flows into the sea. After enrichment by solid-phase extraction the compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In addition to the target compounds a screening analysis of the extracts revealed the presence of other wastewater related pollutants (caffeine, flame retardants, antioxidants). Several of the investigated substances demonstrate a surprising persistence in the aquatic environment. This emphasizes the need for a broader view on the concept of persistence by taking into account the recharge/loading rate in addition to removal mechanisms; transformation, volatility and physical sequestration by solids and the influence of different environmental media (Soil organic matter, mineralogy, macroscopic physical properties etc) in various hydrological systems.

[Place of persistence trouble during oral contraception and subsequent use of emergency contraception].

PubMed

Jamin, C; Lachowsky, M

2015-10-01

In order to improve the understanding of hormonal contraceptive failures, this study evaluates the persistence of oral contraception and the use of emergency contraception (EC) during persistence incidents. We made the hypothesis of the existence of a strong link between the risk of unplanned pregnancies and these two parameters. In this study, we also evaluated women's perception of EC in order to elucidate the reasons of EC insufficient use. One survey was carried out on Internet on a representative sample of women, aged 16-45. In this survey, 3775 French women were interviewed (source-population). We defined a target population of 2415 fertile women who had heterosexual intercourse during the last 12 months, and a population of 760 women at risk of unintended pregnancy who had unprotected sexual intercourse during the last 12 months(risk-population). A little more than 30% of the target population, meaning 20% of the source-population (n=745) stopped their contraceptive method temporarily for an average time of two months. Almost 60% of women had a risk of unwanted pregnancy during this period without contraception, which is 59% of the risk-population. Only 20% of women among the population at risk used EC. The main reasons given for EC insufficient use were the misperception of the risk of pregnancy, the lack of knowledge about EC and its way of use. For the first time, this survey shows that 13% of women (of the source population) decide to stop temporarily their contraceptive method for an average time of two months per year. Fifty-nine percent of unplanned pregnancy situations are due to this poor contraception persistence. Although there is a need to reduce the risk of women being at risk, it seems also highly desirable to overcome the consequences of this poor persistence. Giving information about EC and a systematic prescription during contraception consultations would lead to an increased use of EC. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Transmission Dynamics of Methicillin-Resistant Staphylococcus aureus in Pigs

PubMed Central

Crombé, Florence; Argudín, M. Angeles; Vanderhaeghen, Wannes; Hermans, Katleen; Haesebrouck, Freddy; Butaye, Patrick

2013-01-01

From the mid-2000s on, numerous studies have shown that methicillin-resistant Staphylococcus aureus (MRSA), renowned as human pathogen, has a reservoir in pigs and other livestock. In Europe and North America, clonal complex (CC) 398 appears to be the predominant lineage involved. Especially worrisome is its capacity to contaminate humans in close contact with affected animals. Indeed, the typical multi-resistant phenotype of MRSA CC398 and its observed ability of easily acquiring genetic material suggests that MRSA CC398 strains with an increased virulence potential may emerge, for which few therapeutic options would remain. This questions the need to implement interventions to control the presence and spread of MRSA CC398 among pigs. MRSA CC398 shows a high but not fully understood transmission potential in the pig population and is able to persist within that population. Although direct contact is probably the main route for MRSA transmission between pigs, also environmental contamination, the presence of other livestock, the herd size, and farm management are factors that may be involved in the dissemination of MRSA CC398. The current review aims at summarizing the research that has so far been done on the transmission dynamics and risk factors for introduction and persistence of MRSA CC398 in farms. PMID:23518663

COMMUNICATING THE RISKS OF FISH CONSUMPTION

EPA Science Inventory

The primary route of exposure to many persistant bioaccumulating toxins (PBT) such as methyl mercury, PCDs or Dioxins is though foods. Many people, but particularly subsistence fishermen, pregnant women and children, are at high risk for methyl mercury toxicity because of their c...

Chlorinated Persistent Organic Pollutants, Obesity, and Type 2 Diabetes

PubMed Central

Porta, Miquel; Jacobs, David R.; Vandenberg, Laura N.

2014-01-01

Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue. Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D). Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings. This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence. It also discusses how features of POPs can affect inferences in humans. The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures—including organochlorine pesticides and polychlorinated biphenyls—can increase T2D risk in humans. Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations. Differences in the observed shape of the dose-response curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption. Finally, we examine the relationship between POPs and obesity. There is evidence in animal studies that low-dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent. Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs. Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D. Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans. PMID:24483949

Intelligence and Persisting with Medication for Two Years: Analysis in a Randomised Controlled Trial

ERIC Educational Resources Information Center

Deary, Ian J.; Gale, Catharine R.; Stewart, Marlene C. W.; Fowkes, F. Gerald R.; Murray, Gordon D.; Batty, G. David; Price, Jacqueline F.

2009-01-01

The study examined whether verbal intelligence is associated with persisting to take medication for up to two years. The design is a prospective follow-up of compliance with taking medication in high-risk individuals participating in a randomised, placebo-controlled trial set in Central Scotland. Participants were 1993 people aged between 50 and…

Late effect of atomic bomb radiation on myeloid disorders: leukemia and myelodysplastic syndromes.

PubMed

Tsushima, Hideki; Iwanaga, Masako; Miyazaki, Yasushi

2012-03-01

Leukemia was the first malignancy linked to radiation exposure in atomic bomb survivors. Clear evidence of the dose-dependent excess risk of three major types of leukemia (acute lymphocytic leukemia, acute myeloid leukemia [AML], and chronic myeloid leukemia) was found, especially in people exposed at young ages. Such leukemia risks were at their highest in the late 1950s, and declined gradually thereafter over the past 50 years. Findings from recent risk analyses, however, suggest the persistence of AML risk even after 1990, and evidence of increased risk of myelodysplastic syndromes (MDS) due to atomic bomb radiation has recently been shown. High-risk MDS and forms involving complex chromosomal aberrations were found to be much more frequent in people exposed to higher radiation doses. These lines of epidemiological evidence suggest that the risk of radiation-induced hematological malignancies has persisted for six decades since the initial exposure.

Immunology of Bats and Their Viruses: Challenges and Opportunities

PubMed Central

Schountz, Tony

2014-01-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock. PMID:25494448

Immunology of bats and their viruses: challenges and opportunities.

PubMed

Schountz, Tony

2014-12-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.

Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

PubMed Central

Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

2015-01-01

Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment. PMID:26333997

Health risks posed to infants in rural China by exposure to short- and medium-chain chlorinated paraffins in breast milk.

PubMed

Xia, Dan; Gao, Li-Rong; Zheng, Ming-Hui; Li, Jing-Guang; Zhang, Lei; Wu, Yong-Ning; Qiao, Lin; Tian, Qi-Chang; Huang, Hui-Ting; Liu, Wen-Bin; Su, Gui-Jin; Liu, Guo-Rui

2017-06-01

Chlorinated paraffins (CPs) are complex mixtures of synthetic chemicals found widely in environmental matrices. Short-chain CPs (SCCPs) are candidate persistent organic pollutants under the Stockholm Convention. There should be great concern about human exposure to SCCPs. Data on CP concentrations in human breast milk is scarce. This is the first study in which background SCCP and medium-chain CP (MCCP) body burdens in the general rural population of China have been estimated and health risks posed to nursing infants by CPs in breast milk assessed. The concentrations of 48 SCCP and MCCP formula congeners were determined in 24 pooled human milk samples produced from 1412 individual samples from eight provinces in 2007 and 16 provinces in 2011. The samples were analyzed by comprehensive two-dimensional gas chromatography electron capture negative ionization high-resolution time-of-flight mass spectrometry. The median SCCP and MCCP concentrations were 303 and 35.7ngg -1 lipid weight, respectively, for the 2007 samples and 360 and 45.4ngg -1 lipid weight, respectively, for the 2011 samples. The C 10 and C 14 homologs were the dominant CP carbon-chain-length groups, contributing 51% and 82% of the total SCCP and MCCP concentrations, respectively. There are probably multiple CP sources to the general Chinese population and numerous exposure pathways. The median estimated daily SCCP and MCCP intakes for nursing infants were 1310 and 152ngkg -1 d -1 , respectively, in 2007 and 1520 and 212ngkg -1 d -1 , respectively, in 2011. SCCPs do not currently pose significant risks to infants in China. However, it is necessary to continuously monitor CP concentrations and health risks because CP concentrations in Chinese human breast milk are increasing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evolving Righteousness in a Corrupt World

PubMed Central

Duéñez-Guzmán, Edgar A.; Sadedin, Suzanne

2012-01-01

Punishment offers a powerful mechanism for the maintenance of cooperation in human and animal societies, but the maintenance of costly punishment itself remains problematic. Game theory has shown that corruption, where punishers can defect without being punished themselves, may sustain cooperation. However, in many human societies and some insect ones, high levels of cooperation coexist with low levels of corruption, and such societies show greater wellbeing than societies with high corruption. Here we show that small payments from cooperators to punishers can destabilize corrupt societies and lead to the spread of punishment without corruption (righteousness). Righteousness can prevail even in the face of persistent power inequalities. The resultant righteous societies are highly stable and have higher wellbeing than corrupt ones. This result may help to explain the persistence of costly punishing behavior, and indicates that corruption is a sub-optimal tool for maintaining cooperation in human societies. PMID:22984510

Conservation biogeography of the Cerrado's wild edible plants under climate change: Linking biotic stability with agricultural expansion.

PubMed

de Oliveira, Guilherme; Lima-Ribeiro, Matheus Souza; Terribile, Levi Carina; Dobrovolski, Ricardo; Telles, Mariana Pires de Campos; Diniz-Filho, José Alexandre Felizola

2015-06-01

REMISE OF THE STUDY: Wild edible plants (WEPs) have an important cultural and economic role in human population worldwide. Human impacts are quickly converting natural habitats in agricultural, cattle ranch, and urbanized lands, putting native species on peril of risk of extinction, including some WEPs. Moreover, global climate changes also can pose another threat to species persistency. Here, we established conservation priorities for the Cerrado, a neotropical region in South America with high levels of plant endemism and vulnerability, aiming to assure long-term persistency of 16 most important WEPs. We evaluated these conservation priorities using a conservation biogeography framework using ecological patterns and process at a biogeographical scale to deal with species conservation features. We built ecological niche models for 16 WEPs from Cerrado in the neotropics using climate models for preindustrial, past (Last Glacial Maximum) and future (year 2080) time periods to establish climatically stable areas through time, finding refugias for these WEPs. We used a spatial prioritization algorithm based on the spatial pattern of irreplaceability across the neotropics, aiming to ensure the persistence of at least 25% of range size in climatically stable areas for each WEP, using agricultural models as constraints. The Southeast Cerrado was the most biotically stable and irreplaceable region for the WEPs compared with other areas across the neotropics. Our findings strongly suggest that the Southeast Cerrado should be considered a conservation priority, with new protected areas to be sustainably managed and restored, to guarantee the supply of cultural and ecosystem services provided from the Cerrado's WEPs. © 2015 Botanical Society of America, Inc.

Effects of constant immigration on the dynamics and persistence of stable and unstable Drosophila populations

PubMed Central

Dey, Snigdhadip; Joshi, Amitabh

2013-01-01

Constant immigration can stabilize population size fluctuations but its effects on extinction remain unexplored. We show that constant immigration significantly reduced extinction in fruitfly populations with relatively stable or unstable dynamics. In unstable populations with oscillations of amplitude around 1.5 times the mean population size, persistence and constancy were unrelated. Low immigration enhanced persistence without affecting constancy whereas high immigration increased constancy without enhancing persistence. In relatively stable populations with erratic fluctuations of amplitude close to the mean population size, both low and high immigration enhanced persistence. In these populations, the amplitude of fluctuations relative to mean population size went down due to immigration, and their dynamics were altered to low-period cycles. The effects of immigration on the population size distribution and intrinsic dynamics of stable versus unstable populations differed considerably, suggesting that the mechanisms by which immigration reduced extinction risk depended on underlying dynamics in complex ways. PMID:23470546

Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis.

PubMed

Mosmann, Jessica P; Monetti, Marina S; Frutos, Maria C; Kiguen, Ana X; Venezuela, Raul F; Cuffini, Cecilia G

2015-01-01

Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from Cordoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.

Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders.

PubMed

Keller, Matthew C

2018-05-07

Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of evolutionary explanations that have been used to help understand human psychiatric disorders. First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations-natural selection-is less useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection, offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable using whole-genome data. Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness, anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of evidence for this hypothesis. Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating new, testable hypotheses and understanding how best to design studies and analyze data.

Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol

PubMed Central

Lou, Sijia; Zelenyuk, Alla; Easter, Richard C.; Corley, Richard A.; Thrall, Brian D.; Rasch, Philip J.; Fast, Jerome D.; Massey Simonich, Staci L.; Tao, Shu

2017-01-01

Polycyclic aromatic hydrocarbons (PAHs) have toxic impacts on humans and ecosystems. One of the most carcinogenic PAHs, benzo(a)pyrene (BaP), is efficiently bound to and transported with atmospheric particles. Laboratory measurements show that particle-bound BaP degrades in a few hours by heterogeneous reaction with ozone, yet field observations indicate BaP persists much longer in the atmosphere, and some previous chemical transport modeling studies have ignored heterogeneous oxidation of BaP to bring model predictions into better agreement with field observations. We attribute this unexplained discrepancy to the shielding of BaP from oxidation by coatings of viscous organic aerosol (OA). Accounting for this OA viscosity-dependent shielding, which varies with temperature and humidity, in a global climate/chemistry model brings model predictions into much better agreement with BaP measurements, and demonstrates stronger long-range transport, greater deposition fluxes, and substantially elevated lung cancer risk from PAHs. Model results indicate that the OA coating is more effective in shielding BaP in the middle/high latitudes compared with the tropics because of differences in OA properties (semisolid when cool/dry vs. liquid-like when warm/humid). Faster chemical degradation of BaP in the tropics leads to higher concentrations of BaP oxidation products over the tropics compared with higher latitudes. This study has profound implications demonstrating that OA strongly modulates the atmospheric persistence of PAHs and their cancer risks. PMID:28115713

Global long-range transport and lung cancer risk from polycyclic aromatic hydrocarbons shielded by coatings of organic aerosol

NASA Astrophysics Data System (ADS)

Shrivastava, Manish; Lou, Silja; Zelenyuk, Alla; Easter, Richard C.; Corley, Richard A.; Thrall, Brian D.; Rasch, Philip J.; Fast, Jerome D.; Massey Simonich, Staci L.; Shen, Huizhong; Tao, Shu

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs) have toxic impacts on humans and ecosystems. One of the most carcinogenic PAHs, benzo(a)pyrene (BaP), is efficiently bound to and transported with atmospheric particles. Laboratory measurements show that particle-bound BaP degrades in a few hours by heterogeneous reaction with ozone, yet field observations indicate BaP persists much longer in the atmosphere, and some previous chemical transport modeling studies have ignored heterogeneous oxidation of BaP to bring model predictions into better agreement with field observations. We attribute this unexplained discrepancy to the shielding of BaP from oxidation by coatings of viscous organic aerosol (OA). Accounting for this OA viscosity-dependent shielding, which varies with temperature and humidity, in a global climate/chemistry model brings model predictions into much better agreement with BaP measurements, and demonstrates stronger long-range transport, greater deposition fluxes, and substantially elevated lung cancer risk from PAHs. Model results indicate that the OA coating is more effective in shielding BaP in the middle/high latitudes compared with the tropics because of differences in OA properties (semisolid when cool/dry vs. liquid-like when warm/humid). Faster chemical degradation of BaP in the tropics leads to higher concentrations of BaP oxidation products over the tropics compared with higher latitudes. This study has profound implications demonstrating that OA strongly modulates the atmospheric persistence of PAHs and their cancer risks.

Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model

PubMed Central

Brake, Tiffany; Lambert, Paul F.

2005-01-01

Cervical cancer is a leading cause of death by cancer among women worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer, but other factors likely contribute to cervical cancer, because these cancers commonly arise decades after initial exposure to HPV. Estrogen is thought to be one such cofactor; however, its temporal requirements in human cervical cancer are not known. Here we evaluate the temporal requirements of estrogen in cervical carcinogenesis in a mouse model for HPV-associated cervical cancer. Tumors arising in HPV16 transgenic mice treated with estrogen for 9 months were greatly increased in their size compared with tumors developing after 6 months of estrogen treatment. HPV16 transgenic mice treated 6 months with estrogen followed by 3 months without exogenous estrogen had significantly fewer tumors and the tumors were smaller and less aggressive than those arising in mice treated the full 9 months. Importantly, cervical cancers that arose in the mice treated the first 6 of 9 months with estrogen must have regressed, based upon the reduced incidence of cancers in these mice compared with those treated for 6 months with estrogen, then immediately analyzed. We conclude that estrogen plays a critical role not only in the genesis of cervical cancer but also in its persistence and continued development in this mouse model. These findings raise the clinically relevant possibility that, if human cervical cancer has a similar dependence on estrogen for continued tumor growth, then antiestrogen therapy may be effective in the treatment of cervical cancer. PMID:15699322

Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma: insights from the TENOR study.

PubMed

Lee, June H; Haselkorn, Tmirah; Borish, Larry; Rasouliyan, Lawrence; Chipps, Bradley E; Wenzel, Sally E

2007-12-01

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. Data from adult patients (>or= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >or= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio

Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

PubMed Central

2010-01-01

Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence. Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women. PMID:21070660

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients

PubMed Central

Osman, Marwan; Benamrouz, Sadia; Guyot, Karine; Baydoun, Martha; Frealle, Emilie; Chabe, Magali; Gantois, Nausicaa; Delaire, Baptiste; Goffard, Anne; Aoun, Albert; Jurdi, Nawaf; Dabboussi, Fouad; Even, Gael; Slomianny, Christian; Gosset, Pierre; Hamze, Monzer; Creusy, Colette; Viscogliosi, Eric

2017-01-01

Background The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients. Methodology and principal findings Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65–9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44–89.02, P = 0.003). Conclusions This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease. PMID:29261714

Evaluation of the Persistence of Infectious Human Noroviruses on Food Surfaces by Using Real-Time Nucleic Acid Sequence-Based Amplification▿

PubMed Central

Lamhoujeb, Safaa; Fliss, Ismail; Ngazoa, Solange E.; Jean, Julie

2008-01-01

Noroviruses (NoV) are the major cause of nonbacterial gastroenteritis. However, there is no published study to ascertain their survival on foodstuffs which are directly related to human health risk. In the present study, we developed a rapid, simple, and sensitive real-time nucleic acid sequence-based amplification (NASBA) combined with an enzymatic treatment for distinguishing infectious from noninfectious human NoV. The developed method was validated using spiked ready-to-eat food samples. When feline calicivirus (FCV) was used as a NoV surrogate in the preliminary assays, it appeared more sensitive to heat inactivation and enzymatic pretreatment than the human NoV. This suggests that FCV may not be an ideal model for studying NoV. Our results reveal clearly that the developed enzymatic pretreatment/real-time NASBA combination successfully distinguished the infectious from heat-inactivated NoV. Moreover, we demonstrate that NoV survived for at least 10 days on refrigerated ready-to-eat foods, such as lettuce and turkey. However, the survival rate was higher on turkey than on lettuce, probably because of their different surface natures. The approach developed in this study may be suitable for more in-depth studies of the persistence and inactivation of human NoV and may be applied to other nonculturable RNA viruses. Moreover, the evaluation of infectious NoV survival provided valuable information concerning its persistence on ready-to-eat food. PMID:18378643

Adverse life events as risk factors for behavioural and emotional problems in a 7-year follow-up of a population-based child cohort.

PubMed

Rasmussen, Cathrine Skovmand; Nielsen, Louise Gramstrup; Petersen, Dorthe Janne; Christiansen, Erik; Bilenberg, Niels

2014-04-01

The aim of the study was to identify risk factors for significant changes in emotional and behavioural problem load in a community-based cohort of Danish children aged 9-16 years, the risk factors being seven parental and two child-related adverse life events. Data on emotional and behavioural problems was obtained from parents filling in the Child Behavior Checklist (CBCL) when the child was 8-9 and again when 15 years old. Data on risk factors was drawn from Danish registers. Analysis used was logistic regression for crude and adjusted change. Parental divorce significantly raised the odds ratio of an increase in emotional and behavioural problems; furthermore, the risk of deterioration in problem behaviour rose significantly with increasing number of adverse life events. By dividing the children into four groups based on the pathway in problem load (increasers, decreasers, high persisters and low persisters), we found that children with a consistently high level of behavioural problems also had the highest number of adverse life events compared with any other group. Family break-up was found to be a significant risk factor. This supports findings in previous studies. The fact that no other risk factor proved to be of significance might be due to lack of power in the study. Children experiencing high levels of adverse life events are at high risk of chronic problem behaviour. Thus these risk factors should be assessed in daily clinical practice.

The art of persistence—the secrets to Burkholderia chronic infections

PubMed Central

Lewis, Eric R. G.; Torres, Alfredo G.

2016-01-01

The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia. Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them. PMID:27440810

Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial.

PubMed

Wai, Katherine C; Hibbs, Anna M; Steurer, Martina A; Black, Dennis M; Asselin, Jeanette M; Eichenwald, Eric C; Ballard, Philip L; Ballard, Roberta A; Keller, Roberta L

2018-04-04

To evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship. We assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis. Of 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively. Among former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences. ClinicalTrials.gov: NCT01022580. Copyright © 2018 Elsevier Inc. All rights reserved.

Arsenic in agricultural soils across China: Distribution pattern, accumulation trend, influencing factors, and risk assessment.

PubMed

Zhou, Yuting; Niu, Lili; Liu, Kai; Yin, Shanshan; Liu, Weiping

2018-03-01

Arsenic (As) in the environment is of concern due to its strong toxicity and high risks to the ecosystems and humans. In this study, soil samples across China collected in 2011 and 2016 were used to determine the concentrations of arsenic in arable soils. The median concentration of arsenic in surface soils was 9.7mg/kg. The inventory of arsenic in the Chinese agricultural surface soils was estimated to be 3.7×10 6 tons. In general, arsenic contamination was found higher in South and Northeast China than in other regions, with means of 18.7 and 15.8mg/kg, respectively. Vertically, arsenic concentrations were higher in top layer (0-15cm) soils (median of 9.8mg/kg) and decreased with soil depth (medians of 8.9mg/kg at 15-30cm and 8.0mg/kg at 30-45cm). By comparing with published data, an increasing accumulation trend over the past decades was found and this enhancement was positively related with the long-term application of fertilizers in agricultural practice, especially phosphate fertilizers. Soil pH was found to affect the movement of arsenic in soil, and high-pH conditions enhanced the pool of arsenic. The ecological risk assessment revealed that arsenic in Chinese agricultural soil posed a low risk to the ecosystem. Regarding human health, the mean hazard indices (HIs) of arsenic were below 1, suggesting an absence of non-carcinogenic risks. In addition, the cancer risks of arsenic in all soil samples were within the acceptable range (below 1×10 -4 ), indicating low to very low risks to the exposed population. Findings from this study are valuable to provide effective management options for risk avoidance and to control the persistent accumulation of arsenic in the agriculture sector across the world. Copyright © 2017 Elsevier B.V. All rights reserved.

PERFLUORINATED COMPOUNDS: EMERGING POPs WITH POTENTIAL IMMUNOTOXICITY

PubMed Central

Corsini, Emanuela; Luebke, Robert W.; Germolec, Dori R.; DeWitt, Jamie C.

2015-01-01

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans. PMID:24503008

Isolation and Characterization of Adenoviruses Persistently Shed from the Gastrointestinal Tract of Non-Human Primates

PubMed Central

Kryazhimskiy, Sergey; Grant, Rebecca; Calcedo, Roberto; Yuan, Xin; Keough, Martin; Sandhu, Arbans; Wang, Qiang; Medina-Jaszek, C. Angelica; Plotkin, Joshua B.; Wilson, James M.

2009-01-01

Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported) together with 22 complete adenovirus genomes available from GenBank revealed that (a) the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b) there was evidence for intraspecies recombination between adenoviruses, and (c) the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors. PMID:19578438

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in transgenic line TgN3261Rpw.

PubMed

Colitz, C M; Malarkey, D E; Woychik, R P; Wilkinson, J E

2000-09-01

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice.

The seaweed fly (Coelopidae) can facilitate environmental survival and transmission of E. coli O157 at sandy beaches.

PubMed

Swinscoe, Isobel; Oliver, David M; Gilburn, Andre S; Quilliam, Richard S

2018-06-19

The sustainable management of recreational beaches is essential for minimising risk of human exposure to microbial pathogens whilst simultaneously maintaining valuable ecosystem services. Decaying seaweed on public beaches is gaining recognition as a substrate for microbial contamination, and is a potentially significant reservoir for human pathogens in close proximity to beach users. Closely associated with beds of decaying seaweed are dense populations of the seaweed fly (Coelopidae), which could influence the spatio-temporal fate of seaweed-associated human pathogens within beach environments. Replicated mesocosms containing seaweed inoculated with a bioluminescent strain of the zoonotic pathogen E. coli O157:H7, were used to determine the effects of two seaweed flies, Coelopa frigida and C. pilipes, on E. coli O157:H7 survival dynamics. Multiple generations of seaweed flies and their larvae significantly enhanced persistence of E. coli O157:H7 in simulated wrack habitats, demonstrating that both female and male C. frigida flies are capable of transferring E. coli O157:H7 between individual wrack beds and into the sand. Adult fly faeces can contain significant concentrations of E. coli O157:H7, which suggests they are capable of acting as biological vectors and bridge hosts between wrack habitats and other seaweed fly populations, and facilitate the persistence and dispersal of E. coli O157:H7 in sandy beach environments. This study provides the first evidence that seaweed fly populations inhabiting natural wrack beds contaminated with the human pathogen E. coli O157:H7 have the capacity to amplify the hazard source, and therefore potential transmission risk, to beach users exposed to seaweed and sand in the intertidal zone. The risk to public health from seaweed flies and decaying wrack beds is usually limited by human avoidance behaviour; however, seaweed fly migration and nuisance inland plagues in urban areas could increase human exposure routes beyond the beach environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Self-injury, aggression and destruction in children with severe intellectual disability: Incidence, persistence and novel, predictive behavioural risk markers.

PubMed

Davies, L E; Oliver, C

2016-01-01

A risk informed, early intervention strategy for self-injurious, aggressive and destructive behaviours in children with severe intellectual disability is gaining support. The aims of this study were to establish the cumulative incidence and persistence of self-injury, aggression and destruction and the relationship between these behaviours and two potentially predictive behavioural risk markers (repetitive behaviour, and impulsivity and overactivity) in children at high risk. In a longitudinal design self-injury, aggression and destruction were assessed by teachers of 417 children with severe intellectual disability on two occasions separated by 15-18 months. Aggression, destruction and self-injury were persistent (69%, 57% and 58% respectively). Repetitive and restricted behaviours and interests (RRBI) and overactivity/impulsivity (O/I) were significantly associated with aggression (O/I OR=1.291, p<.001), destruction (RRBI OR 1.201, p=.013; O/I OR 1.278, p<.001) and/or self-injury (RRBI, OR 1.25, p=.004; O/I OR=1.117, p<.001). The relative risk of the cumulative incidence of self-injury, aggression and destruction was significantly increased by repetitive and restricted behaviours and interests (self-injury 2.66, destruction 2.16) and/or overactivity/impulsivity (aggression 2.42, destruction 2.07). The results provide evidence that repetitive and restricted behaviours and interests, and overactivity/impulsivity, are risk markers for the onset of self-injury, aggression and destruction within the already high risk group of children with severe intellectual disability. Copyright © 2015 Elsevier Ltd. All rights reserved.

HUMAN CAPITAL GROWTH AND POVERTY: EVIDENCE FROM ETHIOPIA AND PERU

PubMed Central

ATTANASIO, ORAZIO; MEGHIR, COSTAS; NIX, EMILY; SALVATI, FRANCESCA

2017-01-01

In this paper we use high quality data from two developing countries, Ethiopia and Peru, to estimate the production functions of human capital from age 1 to age 15. We characterize the nature of persistence and dynamic complementarities between two components of human capital: health and cognition. We also explore the implications of different functional form assumptions for the production functions. We find that more able and higher income parents invest more, particularly at younger ages when investments have the greatest impacts. These differences in investments by parental income lead to large gaps in inequality by age 8 that persist through age 15. PMID:28579736

Cadmium Exposure and Pancreatic Cancer in South Louisiana

PubMed Central

Luckett, Brian G.; Su, L. Joseph; Rood, Jennifer C.; Fontham, Elizabeth T. H.

2012-01-01

Cadmium has been hypothesized to be a pancreatic carcinogen. We test the hypothesis that cadmium exposure is a risk factor for pancreatic cancer with a population-based case-control study sampled from a population with persistently high rates of pancreatic cancer (south Louisiana). We tested potential dietary and nondietary sources of cadmium for their association with urinary cadmium concentrations which reflect long-term exposure to cadmium due to the accumulation of cadmium in the kidney cortex. Increasing urinary cadmium concentrations were significantly associated with an increasing risk of pancreatic cancer (2nd quartile OR = 3.34, 3rd = 5.58, 4th = 7.70; test for trend P ≤ 0.0001). Potential sources of cadmium exposure, as documented in the scientific literature, found to be statistically significantly associated with increased risk of pancreatic cancer included working as a plumber, pipefitter or welder (OR = 5.88) and high consumption levels of red meat (4th quartile OR = 6.18) and grains (4th quartile OR = 3.38). Current cigarette smoking, at least 80 pack years of smoking, occupational exposure to cadmium and paints, working in a shipyard, and high consumption of grains were found to be statistically significantly associated with increased concentrations of urinary cadmium. This study provides epidemiologic evidence that cadmium is a potential human pancreatic carcinogen. PMID:23319964

Timing and Duration of Traffic-related Air Pollution Exposure and the Risk for Childhood Wheeze and Asthma

PubMed Central

Brunst, Kelly J.; Brokamp, Cole; Bernstein, David; Reponen, Tiina; Lockey, James; Khurana Hershey, Gurjit K.; Levin, Linda; Grinshpun, Sergey A.; LeMasters, Grace

2015-01-01

Rationale: The timing and duration of traffic-related air pollution (TRAP) exposure may be important for childhood wheezing and asthma development. Objectives: We examined the relationship between TRAP exposure and longitudinal wheezing phenotypes and asthma at age 7 years. Methods: Children completed clinical examinations annually from age 1 year through age 4 years and age 7 years. Parental-reported wheezing was assessed at each age, and longitudinal wheezing phenotypes (early-transient, late-onset, persistent) and asthma were defined at age 7 years. Participants’ time-weighted exposure to TRAP, from birth through age 7 years, was estimated using a land-use regression model. The relationship between TRAP exposure and wheezing phenotypes and asthma was examined. Measurements and Main Results: High TRAP exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] = 1.64; 95% confidence interval [CI], 1.04–2.57 and aOR = 2.31; 95% CI, 1.28–4.15, respectively); exposure from birth to age 1 year and age 1 to 2 years was also associated with persistent wheeze. Only children with high average TRAP exposure from birth through age 7 years were at significantly increased risk for asthma (aOR = 1.71; 95% CI, 1.01–2.88). Conclusions: Early-life exposure to TRAP is associated with increased risk for persistent wheezing, but only long-term exposure to high levels of TRAP throughout childhood was associated with asthma development. PMID:26106807

The fanconi anemia pathway limits human papillomavirus replication.

PubMed

Hoskins, Elizabeth E; Morreale, Richard J; Werner, Stephen P; Higginbotham, Jennifer M; Laimins, Laimonis A; Lambert, Paul F; Brown, Darron R; Gillison, Maura L; Nuovo, Gerard J; Witte, David P; Kim, Mi-Ok; Davies, Stella M; Mehta, Parinda A; Butsch Kovacic, Melinda; Wikenheiser-Brokamp, Kathryn A; Wells, Susanne I

2012-08-01

High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population.

Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat?

PubMed Central

Diav-Citrin, Orna; Ornoy, Asher

2012-01-01

Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed during pregnancy. The purpose of the present paper is to summarize and evaluate the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. The literature has been inconsistent. Although most studies have not shown an increase in the overall risk of major malformations, several studies have suggested that SSRIs may be associated with a small increased risk for cardiovascular malformations. Others have noted associations between SSRIs and specific types of rare major malformations. In some studies, there appears to be a small increased risk for miscarriages, which may be associated with the underlying maternal condition. Neonatal effects have been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Persistent pulmonary hypertension of the newborn has also been described with an absolute risk of <1%. The risk associated with treatment discontinuation, for example, higher frequency of relapse and increased risk of preterm delivery, should also be considered. The overall benefit of treatment seems to outweigh the potential risks. PMID:22190957

Campus Employment as a High Impact Practice: Relationship to Academic Success and Persistence of First-Generation College Students

ERIC Educational Resources Information Center

Savoca, Marianna

2016-01-01

The double burden of spiraling costs and limited financial aid has prompted more college students to work more hours than ever. Yet, working more hours can be detrimental to students' academic success and persistence, and first-generation college students are at even higher risk. While institutions cannot control off campus employment students…

Gene–Dairy Food Interactions and Health Outcomes: A Review of Nutrigenetic Studies

PubMed Central

Pasin, Gonca

2017-01-01

Each person differs from the next by an average of over 3 million genetic variations in their DNA. This genetic diversity is responsible for many of the interindividual differences in food preferences, nutritional needs, and dietary responses between humans. The field of nutrigenetics aims to utilize this type of genetic information in order to personalize diets for optimal health. One of the most well-studied genetic variants affecting human dietary patterns and health is the lactase persistence mutation, which enables an individual to digest milk sugar into adulthood. Lactase persistence is one of the most influential Mendelian factors affecting human dietary patterns to occur since the beginning of the Neolithic Revolution. However, the lactase persistence mutation is only one of many mutations that can influence the relationship between dairy intake and disease risk. The purpose of this review is to summarize the available nutrigenetic literature investigating the relationships between genetics, dairy intake, and health outcomes. Nonetheless, the understanding of an individual’s nutrigenetic responses is just one component of personalized nutrition. In addition to nutrigenetic responses, future studies should also take into account nutrigenomic responses (epigenomic, transcriptomic, proteomic, metabolomic), and phenotypic/characteristic traits (age, gender, activity level, disease status, etc.), as these factors all interact with diet to influence health. PMID:28684688

The Multiple Carbohydrate Binding Specificities of Helicobacter pylori

NASA Astrophysics Data System (ADS)

Teneberg, Susann

Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of peptic ulcer disease and gastric cancer. Adhesion of microbes to the target tissue is an important determinant for successful initiation, establishment and maintenance of infection, and a variety of different candidate carbohydrate receptors for H. pylori have been identified. Here the different the binding specifities, and their potential role in adhesion to human gastric epithelium are described. Finally, recent findings on the roles of sialic acid binding SabA adhesin in interactions with human neutrophils and erythrocytes are discussed.

[Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

PubMed

2016-01-01

LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. Copyright © 2015. Published by Elsevier España.

Academic Outcomes of High Risk Students. Data Notes. Volume 4, Number 4, July/August 2009

ERIC Educational Resources Information Center

Clery, Sue

2009-01-01

Many postsecondary students possess risk factors that are associated with decreased rates of persistence and credential completion. Traditional students, those without risk factors and with greater rates of postsecondary success are in the minority. Using data from Achieving the Dream: Community College Count, this issue of "Data Notes" examines…

T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection.

PubMed

Wang, George C; Dash, Pradyot; McCullers, Jonathan A; Doherty, Peter C; Thomas, Paul G

2012-04-04

A diverse T cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8⁺ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8⁺ T cells recovered directly ex vivo. We found that CD8⁺ TCRαβ repertoire diversity, but not the size of the CD8⁺ T cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, our findings indicate that CD8⁺ T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCRα and TCRβ public motif usage, and suggest that a highly diverse TCRαβ repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.

MiRNA-124 is a link between measles virus persistent infection and cell division of human neuroblastoma cells.

PubMed

Naaman, Hila; Rall, Glenn; Matullo, Christine; Veksler-Lublinsky, Isana; Shemer-Avni, Yonat; Gopas, Jacob

2017-01-01

Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.

Anticoagulant rodenticides and wildlife: Introduction

USGS Publications Warehouse

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

Human papillomavirus infection and risk factors in a cohort of Tuscan women aged 18-24: results at recruitment

PubMed Central

2010-01-01

Background There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events. Methods One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy. Results We present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios. Conclusions The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors. PMID:20529280

Predicting Acute and Persistent Neuropathy Associated with Oxaliplatin

PubMed Central

Alejandro, Linh; Behrendt, Carolyn E.; Chen, Kim; Openshaw, Harry; Shibata, Stephen

2014-01-01

Objectives We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy. Methods In a 50% female sample, patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with oxaliplatin 85 mg/m2 every 2 weeks. Accounting for correlation among a subject's cycles, logistic regression estimated per-cycle risk of acute (under 14 days) and persistent (14 days or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy. Results Among mFOLFOX6 recipients (n=50, age 58.9 +10.1 years), 36% received concomitant bevacizumab. Of total cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once: 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body-surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), while risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in Stage IV disease but was associated with persistent neuropathy when administered experimentally in Stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body-surface area, and prior acute neuropathy predicted time to persistent neuropathy. Conclusions Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy. PMID:22547012

Health risk characterization of maximum legal exposures for persistent organic pollutant (POP) pesticides in residential soil: An analysis.

PubMed

Li, Zijian

2018-01-01

Regulations for pesticides in soil are important for controlling human health risk; humans can be exposed to pesticides by ingesting soil, inhaling soil dust, and through dermal contact. Previous studies focused on analyses of numerical standard values for pesticides and evaluated the same pesticide using different standards among different jurisdictions. To understand the health consequences associated with pesticide soil standard values, lifetime theoretical maximum contribution and risk characterization factors were used in this study to quantify the severity of damage using disability-adjusted life years (DALYs) under the maximum "legal" exposure to persistent organic pollutant (POP) pesticides that are commonly regulated by the Stockholm Convention. Results show that computed soil characterization factors for some pesticides present lognormal distributions, and some of them have DALY values higher than 1000.0 per million population (e.g., the DALY for dichlorodiphenyltrichloroethane [DDT] is 14,065 in the Netherlands, which exceeds the tolerable risk of uncertainty upper bound of 1380.0 DALYs). Health risk characterization factors computed from national jurisdictions illustrate that values can vary over eight orders of magnitude. Further, the computed characterization factors can vary over four orders of magnitude within the same national jurisdiction. These data indicate that there is little agreement regarding pesticide soil regulatory guidance values (RGVs) among worldwide national jurisdictions or even RGV standard values within the same jurisdiction. Among these POP pesticides, lindane has the lowest median (0.16 DALYs) and geometric mean (0.28 DALYs) risk characterization factors, indicating that worldwide national jurisdictions provide relatively conservative soil RGVs for lindane. In addition, we found that some European nations and members of the former Union of Soviet Socialist Republics share the same pesticide RGVs and data clusters for the computed characterization factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Assessment of the treatment with imiquimod in persistent infection by human papillomavirus with the polimerase chain reaction method].

PubMed

Hernández Quijano, Tomás; Illanes Aguiar, Berenice; Salas Linares, Natividad; Alarcón Romero, Luz del Carmen; Hernández Valencia, Marcelino

2006-06-01

Molecular studies have shown that oncogenic genotypes of human papillomavirus (HPV) are the main risk factor for cervical cancer development. Sub-clinical wound does not cause symptoms and is diagnosed by colposcopy or histology, in addition the latent infection is associated with the presence of DNA of the HPV, but when clinical and histological abnormalities are not presented only molecular techniques can detect this infection. To determine if complementary processing with imiquimod, recent medicament with powerful antiviral activity in vitro as in vivo, reduces the cervical persistence of HPV. This study was carried out with 87 patients, who had antecedents of HPV cervical and intraepithelial wound with low degree. Patients were divided as follows: treated with cryotherapy, cervical loop electrosurgical and imiquimod, all with diagnosis by cervical cytology, colposcopy and polymerase chain reaction (PCR) for HPV. At 3, 6 and 12 months after the processing, PCR, cervical cytology and colposcopy control were carried out again. Out of the 87 patients studied, 11% (10) patients treated with cervical cytology were positive for VPH; with colposcopy 8% (7) of patients and with PCR 40% (34) of patients; decreased persistence with combined methods of loop and imiquimod was obtained in 29% (5) patients; however, when utilized imiquimod alone, there were 55% (11) patients with persistence determined by PCR method. Imiquimod appears to be beneficial in 45% of the patients, in contrast with efficacy reported until 85% in genitals and annals warts, in addition, the capacity of eliminating the viruses has been shown, therefore it is possible that its potential effect could be observed long-time. It is evident that the percentages of viral detection are improved for PCR method, compared with indirect methods as cervical cytology and colposcopy, which is favorable when virus serotypes are of high degree of transformation and ablative methods should be conservatives due to fertility motives.

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

PubMed

Rohde, Rebecca L; Adjei Boakye, Eric; Christopher, Kara M; Geneus, Christian J; Walker, Ronald J; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-06-14

There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population. Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion. A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion. HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human health risk assessment in relation to environmental pollution of two artificial freshwater lakes in The Netherlands.

PubMed

Albering, H J; Rila, J P; Moonen, E J; Hoogewerff, J A; Kleinjans, J C

1999-01-01

A human health risk assessment has been performed in relation to recreational activities on two artificial freshwater lakes along the river Meuse in The Netherlands. Although the discharges of contaminants into the river Meuse have been reduced in the last decades, which is reflected in decreasing concentrations of pollutants in surface water and suspended matter, the levels in sediments are more persistent. Sediments of the two freshwater lakes appear highly polluted and may pose a health risk in relation to recreational activities. To quantify health risks for carcinogenic (e.g., polycyclic aromatic hydrocarbons) as well as noncarcinogenic compounds (e.g., heavy metals), an exposure assessment model was used. First, we used a standard model that solely uses data on sediment pollution as the input parameter, which is the standard procedure in sediment quality assessments in The Netherlands. The highest intake appeared to be associated with the consumption of contaminated fish and resulted in a health risk for Pb and Zn (hazard index exceeded 1). For the other heavy metals and for benzo(a)pyrene, the total averaged exposure levels were below levels of concern. Secondly, input data for a more location-specific calculation procedure were provided via analyses of samples from sediment, surface water, and suspended matter. When these data (concentrations in surface water) were taken into account, the risk due to consumption of contaminated fish decreased by more than two orders of magnitude and appeared to be negligible. In both exposure assessments, many assumptions were made that contribute to a major degree to the uncertainty of this risk assessment. However, this health risk evaluation is useful as a screening methodology for assessing the urgency of sediment remediation actions.

Human health risk assessment in relation to environmental pollution of two artificial freshwater lakes in The Netherlands.

PubMed Central

Albering, H J; Rila, J P; Moonen, E J; Hoogewerff, J A; Kleinjans, J C

1999-01-01

A human health risk assessment has been performed in relation to recreational activities on two artificial freshwater lakes along the river Meuse in The Netherlands. Although the discharges of contaminants into the river Meuse have been reduced in the last decades, which is reflected in decreasing concentrations of pollutants in surface water and suspended matter, the levels in sediments are more persistent. Sediments of the two freshwater lakes appear highly polluted and may pose a health risk in relation to recreational activities. To quantify health risks for carcinogenic (e.g., polycyclic aromatic hydrocarbons) as well as noncarcinogenic compounds (e.g., heavy metals), an exposure assessment model was used. First, we used a standard model that solely uses data on sediment pollution as the input parameter, which is the standard procedure in sediment quality assessments in The Netherlands. The highest intake appeared to be associated with the consumption of contaminated fish and resulted in a health risk for Pb and Zn (hazard index exceeded 1). For the other heavy metals and for benzo(a)pyrene, the total averaged exposure levels were below levels of concern. Secondly, input data for a more location-specific calculation procedure were provided via analyses of samples from sediment, surface water, and suspended matter. When these data (concentrations in surface water) were taken into account, the risk due to consumption of contaminated fish decreased by more than two orders of magnitude and appeared to be negligible. In both exposure assessments, many assumptions were made that contribute to a major degree to the uncertainty of this risk assessment. However, this health risk evaluation is useful as a screening methodology for assessing the urgency of sediment remediation actions. Images Figure 1 Figure 2 Figure 3 PMID:9872714

Persistent sample circulation microextraction combined with graphite furnace atomic absorption spectroscopy for trace determination of heavy metals in fish species marketed in Kermanshah, Iran, and human health risk assessment.

PubMed

Safari, Yahya; Karimaei, Mostafa; Sharafi, Kiomars; Arfaeinia, Hossein; Moradi, Masoud; Fattahi, Nazir

2018-06-01

Persistent sample circulation microextraction (PSCME) combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed as a high pre-concentration technique for the determination of heavy metals in fish species. In this method, a few microliters of organic solvent (40.0 µL carbon tetrachloride) was transferred to the bottom of a conical sample cup. Then 10.0 mL of aqueous solution was transformed to fine droplets while passing through the organic solvent. At this stage, metal-ligand hydrophobic complex was extracted into the organic solvent. After extraction, 20 µL of extraction solvent was injected into the graphite tube using an auto-sampler. Under optimal conditions, enrichment factors and enhancement factor were in the range of 180-240 and 155-214, respectively. The calibration curves were linear in the range of 0.03-200 µg kg -1 and the limits of detection (LODs) were in the range of 0.01-0.05 µg kg -1 . Repeatability (intra-day) and reproducibility (inter-day) for 0.50 µg L -1 Hg and 0.10 µg L -1 Cd and Pb were in the range of 3.1-4.2% (n = 7) and 4.3-6.1% (n = 7), respectively. Potential human health risk assessment was conducted by calculating estimated weekly intake (EWI) of the metals from eating fish and comparison of these values with provisional tolerable weekly intake (PTWI) values. EWI data for the studied metals through fish consumption were lower than the PTWI values. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Benchmarking Anthropogenic Heavy Metals Emissions: Australian and Global Urban Environmental Health Risk Based Indicators of Sustainability

ERIC Educational Resources Information Center

Dejkovski, Nick

2016-01-01

In Australia, the impacts of urbanisation and human activity are evident in increased waste generation and the emissions of metals into the air, land or water. Metals that have accumulated in urban soils almost exclusively anthropogenically can persist for long periods in the environment. Anthropogenic waste emissions containing heavy metals are a…

Mathematical modeling of Chikungunya fever control

NASA Astrophysics Data System (ADS)

Hincapié-Palacio, Doracelly; Ospina, Juan

2015-05-01

Chikungunya fever is a global concern due to the occurrence of large outbreaks, the presence of persistent arthropathy and its rapid expansion throughout various continents. Globalization and climate change have contributed to the expansion of the geographical areas where mosquitoes Aedes aegypti and Aedes albopictus (Stegomyia) remain. It is necessary to improve the techniques of vector control in the presence of large outbreaks in The American Region. We derive measures of disease control, using a mathematical model of mosquito-human interaction, by means of three scenarios: a) a single vector b) two vectors, c) two vectors and human and non-human reservoirs. The basic reproductive number and critical control measures were deduced by using computer algebra with Maple (Maplesoft Inc, Ontario Canada). Control measures were simulated with parameter values obtained from published data. According to the number of households in high risk areas, the goals of effective vector control to reduce the likelihood of mosquito-human transmission would be established. Besides the two vectors, if presence of other non-human reservoirs were reported, the monthly target of effective elimination of the vector would be approximately double compared to the presence of a single vector. The model shows the need to periodically evaluate the effectiveness of vector control measures.

A nonhuman primate model of chikungunya disease

PubMed Central

Higgs, Stephen; Ziegler, Sarah A.

2010-01-01

Chikungunya disease is a severely debilitating, mosquito-borne, viral illness that has reached epidemic proportions in Africa, Asia, and the islands of the Indian Ocean. A mutation enhancing the ability of the chikungunya virus (CHIKV) to infect and be transmitted by Aedes albopictus has increased the geographical range at risk for infection due to the continuing global spread of this mosquito. Research into disease pathogenesis, vaccine development, and therapeutic design has been hindered by the lack of appropriate animal models of this disease. The meticulous study reported in this issue of the JCI by Labadie et al. is one of the first reports describing CHIKV infection of adult immunocompetent nonhuman primates. Using traditional and modern molecular and immunological approaches, the authors demonstrate that macaques infected with CHIKV are a good model of human CHIKV infection and also show that persistent arthralgia in humans may be caused by persistent CHIKV infection of macrophages. PMID:20179348

Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium.

PubMed

Fahrleitner-Pammer, A; Papaioannou, N; Gielen, E; Feudjo Tepie, M; Toffis, C; Frieling, I; Geusens, P; Makras, P; Boschitsch, E; Callens, J; Anastasilakis, A D; Niedhart, C; Resch, H; Kalouche-Khalil, L; Hadji, P

2017-12-01

Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture. Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence. Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression. The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients. Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Different aspects of virus persistence (review).

PubMed

Barnabishvili, N; Topuria, T; Gamtsemlidze, P; Topuria, M

2012-05-01

The article reviews different aspects of virus persistence in human organism. Persistence is a capability acquired and strengthened in the process of evolution of many viruses that is the means of maintenance of species. Viruses of measles, poliomyelitis, mite-like encephalitis, B and C hepatitis, herpes, retro and HIV viruses persist in human organism. Persistence is used by various viruses at various levels; they have different adaptive power and no different pathologic output. But in any case, the necessary condition is that virus should escape from elimination reactions of immune control system. At the same time, the important thing is not to save free virus but to save infected cell. While discussing long-term viral persistence, it is impossible to mark off distinctly the importance of biological participation of macroorganism and provoker in this process. The output of the relationship with infect cell is conditioned on the one hand by permissiveness of cell system, on the other hand by strain pathogen city. The details of attenuation mechanisms of microorganism's different reactions in cases of illness with the same strain are not known well yet. Although, it is clear that in chronic persistence the leading role still has immune system disbalance. In disbalance genesis of immunological equilibration virus-induced changes of immunocompetent cells are high.

The Learning and Competency Development of Master Teachers in Alternative High Schools for At-Risk Youth: A Case Study

ERIC Educational Resources Information Center

Williams, Nida W.

2012-01-01

This qualitative case study was designed to explore how master teachers in transfer high schools learn the competencies they perceive are required to engage at-risk students so that they persist and graduate. The study is based on the following assumptions: (1) The requisite teacher competencies can be defined and identified and, in fact,…

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection

PubMed Central

Gordon, Claire L.; Thome, Joseph J.C.; Igarashi, Suzu

2017-01-01

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. PMID:28130404

Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.

PubMed

Gordon, Claire L; Miron, Michelle; Thome, Joseph J C; Matsuoka, Nobuhide; Weiner, Joshua; Rak, Michael A; Igarashi, Suzu; Granot, Tomer; Lerner, Harvey; Goodrum, Felicia; Farber, Donna L

2017-03-06

T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan. @Gordon et al.

Resisting good news: reactions to breast cancer risk communication.

PubMed

Dillard, Amanda J; McCaul, Kevin D; Kelso, Pamela D; Klein, William M P

2006-01-01

Many women overestimate their percentage risk of breast cancer, even after they have received careful estimates from health professionals. In 2 experiments with 134 young adult women, 6 variables were explored that might influence such risk perception persistence. In Study 1, each of the following explanations was unrelated to persistence: public commitment, self-consistency, and unique causal risk models. In Study 2, two individual difference measures, pessimism and differences in understanding percentages, were unrelated to risk perception persistence. However, providing a "risk anchor" based on downward social comparison processes resulted in better risk acceptance at posttest that persisted at a 2-week follow-up assessment. This article discusses why comparison anchors might be important in risk feedback situations and concludes with recommendations for professionals who wish to provide accurate risk information and have patients adopt that information.

Human papillomavirus-related oropharyngeal cancer.

PubMed

Taberna, M; Mena, M; Pavón, M A; Alemany, L; Gillison, M L; Mesía, R

2017-10-01

High-risk human papillomavirus (HPV) is now recognised as the principal cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in some parts of the world. The primary risk factor for developing HPV-related OPSCC is oral HPV-infection and the majority of oral HPV-infections are acquired by oral sex. Progression into an OPSCC includes persistent infection with evasion of immune response in the microenvironment, the activation of viral early genes (E6, E7) in basal epithelial cells, the deregulation of cell cycle and the accumulation of chromosomal instability. Patients affected by HPV-related OPSCC tend to be younger and have better outcomes. This observation has lead current research to evaluate treatment de-escalation options to reduce long-term associated morbidity. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new options for targeted therapy and immunotherapy approaches. This paper comprehensively reviews our accumulated knowledge regarding the role of HPV in OPSCC spanning from infection to cancer development, including its clinical diagnosis, management and preventive strategies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance

PubMed Central

Raison, Charles L; Miller, Andrew H

2017-01-01

Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome. PMID:27629366

Inactivation of high-risk human papillomaviruses by Holder pasteurization: implications for donor human milk banking.

PubMed

Donalisio, Manuela; Cagno, Valeria; Vallino, Marta; Moro, Guido E; Arslanoglu, Sertac; Tonetto, Paola; Bertino, Enrico; Lembo, David

2014-01-01

Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

The Effect of Cryotherapy on Human Papillomavirus Clearance among HIV-positive Women in Lusaka, Zambia

PubMed Central

Katundu, Katundu; Bateman, Allen C.; Pfaendler, Krista S.; Mwanahamuntu, Mulindi H.; Kapambwe, Sharon; Vermund, Sten H.; Sahasrabuddhe, Vikrant V.; Msadabwe, Susan C.; Stringer, Jeffrey S.A.; Parham, Groesbeck P.; Chibwesha, Carla J.

2015-01-01

Objective We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. Methods We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period following cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. Results A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR]: 28–36 years). The median CD4+ cell count was 350 cells/μL (IQR: 214–470 cells/μL) and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI]: 83–95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 17/67 (25%) cleared their initial hrHPV infection within 12 weeks of treatment, though 65% (11/17) had new hrHPV types detected. Conclusions Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale-up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia. PMID:26125097

The psychological costs and benefits of being highly persistent: personality profiles distinguish mood disorders from anxiety disorders.

PubMed

Cloninger, C Robert; Zohar, Ada H; Hirschmann, Schmuel; Dahan, Dana

2012-02-01

The personality trait of Persistence is highly valued by conscientious overachievers, but it has both psychological costs and benefits. The interactions among multiple personality factors influencing the development of mood and anxiety disorders have been confounded in prior clinical samples, but can be disentangled in terms of their underlying brain circuitry and influence on perception of emotional stimuli. 285 individuals who represented the full range of personality variation in a large sample of adult volunteers from the general community of Israel were selected for follow-up by psychiatric interviews, cognitive testing, and medical examinations. The Temperament and Character Inventory (TCI) measured profiles of traits that distinguished individuals with diagnoses of mood and/or anxiety disorders using linear discriminant analysis and non-linear profile analysis. High Harm Avoidance and low Self-directedness strongly distinguished people with mood and/or anxiety disorders from those with neither. High Persistence distinguished people with only anxiety disorders from those with mood disorders. High Persistence was associated with greater health and happiness overall, but also led to more negative emotions than in people with low Persistence unless they were both unusually tolerant of frustration (i.e., low in Harm Avoidance) and self-accepting of personal limitations (i.e. high in Self-directedness). Subjects were volunteers over 40 years of age at assessment. People who are highly persistent (i.e., persevering, ambitious, perfectionistic) are more likely to have anxiety disorders than mood disorders, even when they have other traits increasing risk for both (i.e., high Harm Avoidance and low Self-directedness). High Persistence increases both positive and negative emotions in most people. However, high Persistence reduces negative emotions and increases positive emotions if a person is easy-going (i.e., "happy-go-lucky" when low in both Harm Avoidance and Self-directedness). Copyright © 2011 Elsevier B.V. All rights reserved.

Definition and preoperative predictors of persistently elevated prostate-specific antigen after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

PubMed

Moreira, Daniel M; Presti, Joseph C; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Freedland, Stephen J

2010-06-01

To define a level of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) that equates with high-risk for disease progression, and to identify preoperative predictors of PSA persistence among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. A total of 901 men treated with RP between 2001 and 2008 were separated into groups based upon PSA nadir within 6 months after RP. We explored the association between nadir groups and time to biochemical recurrence (BCR) using multivariate Cox proportional hazards and determined the preoperative predictors of PSA persistence using logistic regression. Relative to men with undetectable PSA levels, those with a PSA nadir of 0.03 (hazard ratio [HR] 3.88, P < 0.001), 0.04 (HR 4.87, P < 0.001), 0.05-0.09 (HR 12.69, P < 0.001), 0.1-0.19 (HR 13.17, P < 0.001), and 0.2 ng/mL (HR 13.23, P < 0.001) were at increased risk of BCR while men with a nadir of 0.01 (HR 1.36, P = 0.400) and 0.02 (HR 1.64, P = 0.180) were not. Using the PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, 230 men (26%) had persistence. The independent preoperative predictors of PSA persistence were higher body mass index (BMI, P = 0.002), pathological Gleason score (relative to 2-6: 4 + 3-10, P = 0.001) and preoperative PSA level (P < 0.001). Men with a PSA nadir > or = 0.03 ng/mL after RP were at higher risk for BCR. Using a PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, persistence was predicted by known factors associated with aggressive disease (tumour grade, PSA level and BMI). Validation of the present definition in different populations using later end-points remains necessary to assess its prognostic usefulness.

Using Latent Selection Difference to Model Persistence in a Declining Population

PubMed Central

Erickson, Mara E.; Found-Jackson, Christine; Boyce, Mark S.

2014-01-01

Population persistence is a direct measure of the viability of a population. Monitoring the distribution of declining populations or subpopulations over time can yield estimates of persistence, which we show can be modeled as a latent selection difference (LSD) contrasting attributes of sites where populations have persisted versus those that have not. Predicted persistence can be modeled with predictor covariates to identify factors correlated with species persistence. We demonstrate how to model persistence based on changes in occupancy that can include adjustments for detection probability. Using a known historical distribution of the western grebe (Aechmophorus occidentalis), we adapted methods originally developed for occupancy modeling to evaluate how environmental covariates including emergent vegetation and human developments have affected western grebe persistence in Alberta. The relative probability of persistence was correlated with the extent of shoreline bulrush (Scirpus lacustris), which is important vegetation for nesting cover. We also documented that western grebe populations were less likely to persist on lakes in the boreal forest, primarily located on the northern boundary of the species' range. Factors influencing occupancy were different than those determining persistence by western grebes; persistence and occupancy were not correlated. Persistence was more likely on lakes with recreational development, reflecting reliance by grebes on the larger, fish-bearing waterbodies that also are attractive for lakeshore development. Unfortunately, the correlation with recreational development on Alberta's lakes puts grebes at risk for loss of brood-rearing habitats—primary threats to altricial birds—if steps are not taken to prevent disturbance to bulrush stands. Identifying factors related to the persistence of a species—especially one in decline—is a fundamental step in conservation management. PMID:24866172

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury

PubMed Central

Polimanti, Renato; Chen, Chia-Yen; Ursano, Robert J.; Heeringa, Steven G.; Jain, Sonia; Kessler, Ronald C.; Nock, Matthew K.; Smoller, Jordan W.; Sun, Xiaoying; Gelernter, Joel

2017-01-01

Abstract Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS was derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD); and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2 = 1.11%; p = 3.37 × 10−3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839∼Cell adhesion molecule binding (p = 8.9 × 10−6) and GO:0050905∼Neuromuscular process (p = 9.8 × 10−5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases, but mechanisms related to early brain growth may be involved. PMID:27439997

The Impacts of Intrusive Advising on the Persistence of First-Year Science, Technology, and Mathematics Students Identified Using a Risk Prediction Instrument

ERIC Educational Resources Information Center

Campbell, Matthew A.

2013-01-01

Set in a large, urban, public university, this study explores the use of an institutionally specific risk instrument developed to identify students who had a high risk of attrition and the effectiveness of subsequent interventions deployed through advising. Though implemented throughout the institution, this study identified control and treatment…

Eating disorders: Insights from imaging and behavioral approaches to treatment.

PubMed

Stice, Eric; Shaw, Heather

2017-11-01

Understanding factors that contribute to eating disorders, which affect 13% of females, is critical to developing effective prevention and treatment programs. In this paper, we summarize results from prospective studies that identified factors predicting onset and persistence of eating disorders and core symptom dimensions. Next, implications for intervention targets for prevention, and treatment interventions from the risk- and maintenance-factor findings are discussed. Third, given that evidence suggests eating disorders are highly heritable, implying biological risk and maintenance factors for eating disorders, we offer working hypotheses about biological factors that might contribute to eating disorders, based on extant risk factor findings, theory, and cross-sectional studies. Finally, potentially fruitful directions for future research are presented. We suggest that it would be useful for experimental therapeutics trials to evaluate the effects of reducing the risk factors on future onset of eating pathology and on reducing maintenance factors on the risk for persistence of eating pathology, and encourage researchers to utilize prospective high-risk studies so that knowledge regarding potential intervention targets for prevention and treatment interventions for eating disorders can be advanced. Using the most rigorous research designs should help improve the efficacy of prevention and treatment interventions for eating disorders.

Pesticide Exposure, Safety Issues, and Risk Assessment Indicators

PubMed Central

Damalas, Christos A.; Eleftherohorinos, Ilias G.

2011-01-01

Pesticides are widely used in agricultural production to prevent or control pests, diseases, weeds, and other plant pathogens in an effort to reduce or eliminate yield losses and maintain high product quality. Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water. Occupational exposure to pesticides often occurs in the case of agricultural workers in open fields and greenhouses, workers in the pesticide industry, and exterminators of house pests. Exposure of the general population to pesticides occurs primarily through eating food and drinking water contaminated with pesticide residues, whereas substantial exposure can also occur in or around the home. Regarding the adverse effects on the environment (water, soil and air contamination from leaching, runoff, and spray drift, as well as the detrimental effects on wildlife, fish, plants, and other non-target organisms), many of these effects depend on the toxicity of the pesticide, the measures taken during its application, the dosage applied, the adsorption on soil colloids, the weather conditions prevailing after application, and how long the pesticide persists in the environment. Therefore, the risk assessment of the impact of pesticides either on human health or on the environment is not an easy and particularly accurate process because of differences in the periods and levels of exposure, the types of pesticides used (regarding toxicity and persistence), and the environmental characteristics of the areas where pesticides are usually applied. Also, the number of the criteria used and the method of their implementation to assess the adverse effects of pesticides on human health could affect risk assessment and would possibly affect the characterization of the already approved pesticides and the approval of the new compounds in the near future. Thus, new tools or techniques with greater reliability than those already existing are needed to predict the potential hazards of pesticides and thus contribute to reduction of the adverse effects on human health and the environment. On the other hand, the implementation of alternative cropping systems that are less dependent on pesticides, the development of new pesticides with novel modes of action and improved safety profiles, and the improvement of the already used pesticide formulations towards safer formulations (e.g., microcapsule suspensions) could reduce the adverse effects of farming and particularly the toxic effects of pesticides. In addition, the use of appropriate and well-maintained spraying equipment along with taking all precautions that are required in all stages of pesticide handling could minimize human exposure to pesticides and their potential adverse effects on the environment. PMID:21655127

In utero exposure to persistent organic pollutants in relation to testicular cancer risk.

PubMed

Hardell, Lennart; Bavel, Bert; Lindström, Gunilla; Eriksson, Mikael; Carlberg, Michael

2006-02-01

Testicular cancer is the most common tumour type in young men. In Sweden the annual age-adjusted incidence increased significantly by 2.4% during the time period 1984-1993 and during 1994-2003 by 1.4%. Exposure to endocrine disrupting chemicals during the foetal period has been postulated to be a risk factor. In this investigation we studied the concentrations of chlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB), chlordanes and polybrominated diphenylethers (PBDEs) in 58 cases with testicular cancer and 61 age-matched controls. Furthermore, case and control mothers were also asked to participate and 44 case mothers and 45 control mothers agreed. No significant differences were found between cases and controls. Case mothers had in general higher concentrations of these chemicals. For the sum of PCBs an odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-10 was calculated using the median concentration for the controls as cut-off value. For HCB OR = 4.4, CI = 1.7-12 and for PBDE OR = 2.5, 95% CI = 1.02-6.0 were obtained, whereas OR was not significantly increased for pp'-DDE and sum of chlordanes. The cases were born during a period with high concentrations of persistent organic pollutants (POPs) in humans. The decline of the increasing incidence of testicular cancer during recent years may reflect decreasing body burden of certain POPs since the 1980s.

Increased Growth of a Newly Established Mouse Epithelial Cell Line Transformed with HPV-16 E7 in Diabetic Mice.

PubMed

He, Lan; Law, Priscilla T Y; Boon, Siaw Shi; Zhang, Chuqing; Ho, Wendy C S; Banks, Lawrence; Wong, C K; Chan, Juliana C N; Chan, Paul K S

2016-01-01

Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7). This model allowed in-vivo study of interaction between HPV and co-factors of tumorigenesis in syngeneic mice. Diabetes has been shown to increase HPV pathogenicity in different pathological context. Herein, with this newly-established cell line, we uncovered that diabetes promoted CUP-1 xenograft growth in syngeneic db/db mice. In sum, we successfully established a HPV-16 E7 transformed mouse epithelial cell line, which allowed subsequent studies of co-factors in multistep HPV carcinogenesis in an immunocompetent host. More importantly, this study is the very first to demonstrate the promoting effect of diabetes on HPV-associated carcinogenesis in vivo, implicating the importance of cancer surveillance in diabetic environment.

Immunization of HIV-infected adult patients — French recommendations

PubMed Central

Frésard, Anne; Gagneux-Brunon, Amandine; Lucht, Frédéric; Botelho-Nevers, Elisabeth; Launay, Odile

2016-01-01

ABSTRACT Human immunodeficiency virus (HIV)-infected patients remain at increased risk of infection including vaccine-preventable diseases. Vaccines are therefore critical components in the protection of HIV-infected patients from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected patients persist and vaccine coverage in this population could be improved. This article presents the French recommendations regarding immunization of HIV-infected adults in the light of the evidence-based literature on the benefits and the potential risks of vaccines among this vulnerable population. PMID:27409293

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review.

PubMed

Brainard, Julii; Pond, Katherine; Hooper, Lee; Edmunds, Kelly; Hunter, Paul

2016-02-01

The 2013-15 Ebola outbreak was unprecedented due to sustained transmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood.

Persistent hyperphagia in acquired brain injury; an observational case study of patients receiving inpatient rehabilitation.

PubMed

Rowell, Arleen M; Faruqui, Rafey A

2010-01-01

Morbid hunger or persistent hyperphagia is a relatively rare but potentially life threatening complication of acquired brain injury (ABI). This paper presents findings from an observational case study of patients with hyperphagia receiving inpatient neurobehavioural rehabilitation following their acquired brain injury. The case study has utilized dietetic and medical records of identified patients to confirm the persistent and serious nature of this presentation in order to extract important management principles. The findings confirmed that hyperphagia or morbid hunger posed potentially life-threatening health risks to the patient, primarily around weight control and fluid balance, and risks of aggression towards professional and family carers. Pharmacological or behaviour modification interventions were only partially successful in management of this presentation. The study identified a high need for environmental and cue exposure control in management of this condition.

Microbiological diagnosis of human papilloma virus infection.

PubMed

Mateos-Lindemann, Maria Luisa; Pérez-Castro, Sonia; Rodríguez-Iglesias, Manuel; Pérez-Gracia, Maria Teresa

2017-11-01

Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Bacteria as Potential Indicators of Heavy Metal Contamination in a Tropical Mangrove and the Implications on Environmental and Human Health

PubMed Central

De La Rosa-Acosta, Melanie; Jiménez-Collazo, Johannys; Maldonado-Román, Marixa; Malavé-Llamas, Karlo; Musa-Wasil, Juan C.

2017-01-01

Heavy metal (HM) exposure has been associated with human health diseases like cancer, kidney and liver damage, neurological disorders, motor skills, low bone density and learning problems. With the beginning of the industrialization, the heavy metals in high concentration contribute to putting on the risk the humans in the vicinity. Our study site is located in Cataño, Puerto Rico. This is a highly industrialized area. It is surrounded by a recreational park, a rum distillery, two thermoelectric factories, and was impacted by CAPECO (oil refinery) explosion in 2009. Las Cucharillas marsh is part of The San Juan Bay Estuary System, considered as a critical wildlife area. The mangrove marsh has three of the four mangrove species found in PR Laguncularia racemosa, Avicennia germinans and Rhizophora mangle. This study was aimed at seven different heavy metals: Arsenic (As), Cadmium (Cd), Chromium (Cr), Lead (Pb), Zinc (Zn), Mercury (Hg) and Copper (Cu). These metals at high concentrations are of human health concern due to their toxicity, persistence, bioaccumulative and bio magnification potentials. Contamination of surface sediments with HM affects the food chain, starting with marine organisms up to humans. The people who live near the contaminated area and the local fishermen are at high risk of exposure. Studies reveal that certain microorganisms can resist the toxicity of heavy metals even at high concentrations. Our study pretends to exploit the sensitive nature of some bacteria to HM and use them as bioindicators. The objective of this research is to assess the bacterial community on the mangrove marsh, identify these bacteria and correlate bacterial species with the type and concentration of the metals found on the site. Our preliminary results with the BIOLOG® identification were five bacteria that are: Carnobacterium inhibens, Cupriavidus gilardii, Enterococcus maloduratus, Microbacterium flavescens and Ralstonia pickettii. This study will continue with an assessment of the exposure of different concentrations of heavy metals to our identified bacteria and underlying the mechanisms of degradation, magnification and or bioconcentration of these heavy metals. PMID:28835856

Cigarette smoke-induced DNA damage and repair detected by the comet assay in HPV-transformed cervical cells.

PubMed

Moktar, Afsoon; Ravoori, Srivani; Vadhanam, Manicka V; Gairola, C Gary; Gupta, Ramesh C

2009-12-01

Human papillomavirus (HPV) is the causative factor in the development and progression of cervical cancers in >97% of the cases, although insufficient. Epidemiological studies suggest an elevated risk of cervical cancer for cigarette smokers; therefore, we examined cigarette smoke-induced DNA damage and repair in HPV16-transformed human ectocervical cells (ECT1/E6 E7). Cells were treated with cigarette smoke condensate (CSC) for 72 h to assess the formation of single- and double-strand DNA breaks, measured by alkaline and neutral single cell gel electrophoresis assays, respectively. The mean tail length of cells with single-strand breaks was increased by 1.8-, 2.7- and 3.7-fold (p<0.001) after treatment with 4, 8 and 12 microg/ml CSC, respectively. The tail length with double-strand breaks was also increased dose-dependently. These results were further supported by measurement of the mean tail moment: the increase in both single- and double-strand breaks were much more pronounced with increasing concentration of CSC, by up to 23.5-fold (p<0.0001 for both assays). To examine the DNA repair, cells were treated with CSC for 72 h, followed by CSC withdrawal and re-incubation of the cells with fresh medium for 24, 48, or 72 h. Both single- and double-strand DNA breaks were removed during the initial 24 h but no further removal of the damage was observed. Up to 80% of residual single- and double-strand DNA breaks (p<0.05) were found to persist at all CSC concentrations examined. Ellagic acid, a known antioxidant and free-radical scavenger, was found to significantly inhibit DNA breaks induced by CSC. Thus, free radicals may be a plausible source of CSC-induced DNA damage. These data show that CSC-mediated DNA strand breaks are highly persistent, and suggest that persistence of cigarette smoke-associated DNA damage in the presence of HPV infection may lead to increased mutations in cervical cells and ultimately higher cancer risk.

Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases.

PubMed

Wu, Xian-Rui; Remzi, Feza H; Liu, Xiu-Li; Lian, Lei; Stocchi, Luca; Ashburn, Jean; Shen, Bo

2014-11-01

To evaluate the disease course and management strategy for pouch neoplasia. Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high-grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor.

Infection prevention and control during prolonged human space travel.

PubMed

Mermel, Leonard A

2013-01-01

Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

Salmonella Species' Persistence and Their High Level of Antimicrobial Resistance in Flooded Man-Made Rivers in China.

PubMed

Song, Qifa; Zhang, Danyang; Gao, Hong; Wu, Junhua

2018-05-11

Man-made rivers, owing to proximity to human habitats, facilitate transmission of salmonellosis to humans. To determine the contamination situation by Salmonella in flooded man-made rivers and thereafter the exposure risk to public health, we investigated the prevalence of Salmonella species and their antimicrobial resistance in such rivers, as well as the relationship between the incidence of local infectious diarrhea cases and the number of Salmonella isolates from patients. After a heavy flood, 95 isolates of 13 Salmonella serotypes were isolated from 80 river water samples. The two most prevalent serotypes were Typhimurium and Derby. Eight Salmonella serotypes were newly detected after the flood. Overall, 50 isolates were resistant to ampicillin and/or cefotaxime and carried at least bla TEM . Twelve isolates of serotypes Typhimurium, Derby, Rissen, and Indiana were extended-spectrum β-lactamase (ESBL) producing and carried at least one of bla OXA and bla CTX-M-like genes. Twelve isolates of serotypes Typhimurium, Derby, Agona, Rissen, and Indiana were resistant to ciprofloxacin and had gyrA mutations. Isolates of Typhimurium, Derby, and Indiana were concurrently ciprofloxacin resistant and ESBL producing. Pulsed-field gel electrophoresis illustrates the circulation of two dominant clones of Salmonella Typhimurium isolates among patients, river, and food. High prevalence of various highly pathogenic and antimicrobial-resistant Salmonella serotypes shows that man-made rivers are prone to heavy contamination with Salmonella, and as a result put public health at greater risk.

Antibody Levels to Persistent Pathogens and Incident Stroke in Mexican Americans

PubMed Central

Sealy-Jefferson, Shawnita; Gillespie, Brenda W.; Aiello, Allison E.; Haan, Mary N.; Morgenstern, Lewis B.; Lisabeth, Lynda D.

2013-01-01

Background Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by several persistent pathogens. Methodology/Principal Findings Using data from the Sacramento Area Latino Study on Aging (n = 1621), the authors used discrete-time regression to examine associations between stroke risk and (1) immunoglobulin G antibody levels to Helicobacter pylori (H. pylori), Cytomegalovirus, Varicella Zoster Virus, Toxoplasma gondii and Herpes simplex virus 1, and (2) concurrent exposure to several pathogens (pathogen burden), defined as: (a) summed sero-positivity, (b) number of pathogens eliciting high antibody levels, and (c) average antibody level. Models were adjusted for socio-demographics and stroke risk factors. Antibody levels to H. pylori predicted incident stroke in fully adjusted models (Odds Ratio: 1.58; 95% Confidence Interval: 1.09, 2.28). No significant associations were found between stroke risk and antibody levels to the other four pathogens. No associations were found for pathogen burden and incident stroke in fully adjusted models. Conclusions/Significance Our results suggest that exposure to H. pylori may be a stroke risk factor in Mexican Americans and may contribute to ethnic differences in stroke risk given the increased prevalence of exposure to H. pylori in this population. Future studies are needed to confirm this association. PMID:23799066

Treatment simplification in HIV-infected adults as a strategy to prevent toxicity, improve adherence, quality of life and decrease healthcare costs

PubMed Central

Nachega, Jean B; Mugavero, Michael J; Zeier, Michele; Vitória, Marco; Gallant, Joel E

2011-01-01

Since the advent of highly active antiretroviral therapy (HAART), the treatment of human immunodeficiency virus (HIV) infection has become more potent and better tolerated. While the current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than regimens used in the early HAART era, and new agents, formulations and strategies continue to be developed. Simplification of therapy is an option for many patients currently being treated with antiretroviral therapy (ART). The main goals are to reduce pill burden, improve quality of life and enhance medication adherence, while minimizing short- and long-term toxicities, reducing the risk of virologic failure and maximizing cost-effectiveness. ART simplification strategies that are currently used or are under study include the use of once-daily regimens, less toxic drugs, fixed-dose coformulations and induction-maintenance approaches. Improved adherence and persistence have been observed with the adoption of some of these strategies. The role of regimen simplification has implications not only for individual patients, but also for health care policy. With increased interest in ART regimen simplification, it is critical to study not only implications for individual tolerability, toxicity, adherence, persistence and virologic efficacy, but also cost, scalability, and potential for dissemination and implementation, such that limited human and financial resources are optimally allocated for maximal efficiency, coverage and sustainability of global HIV/AIDS treatment. PMID:21845035

Assessment of perception and intention in pesticide purchase in Taiwan.

PubMed

Yeh, Jong Chao; Liao, Chih-Hsiang

2016-05-01

Environmental chemical agents such as pesticides can be purchased easily at a relatively low price, and this has resulted in high concern of environmental toxicity to human health, due to their persistence in various environmental bodies. Hence, this study aims to propose important factors influencing pesticide purchase intentions, including consumers' perceptions of the brand image and the ecological health risk. Since consumers are primary users, the seller knows the product's features but not the psychology of those who purchase it. Therefore, we attempted to clarify purchase intentions and perceptions using structural equation modeling techniques to empirically analyze survey data from 324 pesticide consumers in Taiwan. Our results demonstrate that perceived brand image positively affects perceived quality of a product, whereas perceived risk negatively affects perceived quality and purchase intentions. Furthermore, this study provides evidence that perceived quality positively affects purchase intentions. These relationships suggest that perceived quality mediates both the positive association between brand image and purchase intentions and the negative association between perceived risk and purchase intentions. Based on such outcomes, we propose that consumers need to be informed of pesticides related to costs and environmental benefits.

Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology.

PubMed

Ye, Jing; Cheng, Bei; Cheng, Yi-Fan; Yao, Ye-Li; Xie, Xing; Lu, Wei-Guo; Cheng, Xiao-Dong

Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus (HPV) 16/18 genotyping in 273 patients with LSIL/CIN1. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV (hrHPV) were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases (69.6%) regressed, 37 (13.6%) persisted, and 46 (16.8%) progressed. HPV16/18 positivity (hazard ratio (HR), 2.708; 95% confidence interval (CI), 1.432-5.121; P=0.002) is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.

Presence and Persistence of Zika Virus RNA in Semen, United Kingdom, 2016.

PubMed

Atkinson, Barry; Thorburn, Fiona; Petridou, Christina; Bailey, Daniel; Hewson, Roger; Simpson, Andrew J H; Brooks, Timothy J G; Aarons, Emma J

2017-04-01

Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (56.5%) and was not detected in 9 (39.1%); detection was indeterminate in 1 sample (4.4%). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.

Trichomonas vaginalis and Human Immunodeficiency Virus Coinfection Among Women Under Community Supervision: A Call for Expanded T. vaginalis Screening.

PubMed

Davis, Alissa; Dasgupta, Anindita; Goddard-Eckrich, Dawn; El-Bassel, Nabila

2016-10-01

The United States has a large community supervision population, a growing number of whom are women. Trichomonas vaginalis infection is strongly associated with an increased risk of human immunodeficiency virus (HIV) acquisition and transmission, particularly among women, but there is a paucity of research on HIV and T. vaginalis co-infection among women under community supervision. This article examines the prevalence of T. vaginalis infection and T. vaginalis and HIV coinfection at baseline among women under community supervision in New York City. It also examines the 12-month outcomes of women treated for T. vaginalis. Women received biological tests for HIV and T. vaginalis at baseline and 12 months follow-up. Of the 333 women tested for sexually transmitted infections, 77 women (23.1%) tested positive for T. vaginalis at baseline and 44 (13.3%) were HIV positive. Human immunodeficiency virus-positive women had significantly higher rates of T. vaginalis infection than HIV-negative women (36.4% vs 21.3%, P ≤ 0.05). Sixteen women (4.8%) were coinfected with T. vaginalis and HIV. Of the 77 women who were positive for T. vaginalis infection at baseline, 58 (75.3%) received treatment by a health care provider. Of those who received treatment, 17 (29.3%) tested positive for T. vaginalis at the 12-month follow-up. Given the high prevalence of T. vaginalis among this sample of women, particularly among HIV-positive women, and high levels of reinfection or persistent infection, screening for T. vaginalis among women under community supervision may have a substantial impact on reducing HIV acquisition and transmission among this high-risk population.

Vaccine-derived polioviruses.

PubMed

Agol, Vadim I

2006-06-01

The Sabin oral poliovaccine (OPV) is extremely efficacious and safe, despite its inherent genetic instability. While reversion to nearly wild-type phenotype regularly occurs soon after the onset of OPV reproduction in the gastro-intestinal tract of vaccine recipients or their contacts, this is usually not a big problem, provided the vaccine is used either for mass vaccination or in populations with a relatively high level of anti-polio immunity. However, if these conditions are not met, the vaccine viruses are likely to be converted into highly transmissible agents with a nearly wild-type level of neurovirulence. Moreover, OPV viruses may persist and evolve even in adequately immunized populations. The current strategy for the "endgame" of poliovirus eradication envisions cessation of OPV usage shortly after the last isolation of a wild poliovirus. If implemented, this strategy would result in rapid growth of non-immune human populations at the time when OPV derivatives would very likely be persisting. Therefore, the planned cessation of OPV vaccination is associated with a very high, and in the author's opinion, unacceptable risk of polio outbreaks caused by OPV derivatives. The only currently available tool to curb such outbreaks is OPV, which should have been used at a global scale. Safe discontinuation of OPV vaccination will be possible only after an efficient new vaccine or an anti-poliovirus drug is available. To achieve this goal, stimulation of poliovirus research and elimination of organizational and financial obstacles preventing it are needed.

OPPT workplan assessments for medium and long chain ...

EPA Pesticide Factsheets

MCCPs (C14 – C17) and the C18-20 LCCPs are liquid mixtures of chlorinated alkanes. Short chain chlorinated paraffins (SCCPs, C10-C13) have been the focus of coordinated global action (including by US EPA as an action plan chemical), and MCCPs and LCCPs are alternatives to SCCPs for many applications. In the United States, these substances are typically used in oils and metal working fluids to impart stability during high temperature/pressure operations; in plastics/ rubber (PVC) compounding, paints, coatings, adhesives, and sealants as plasticizers and flame retardants. Other assessments have generally found these chemicals to be highly persistent, and some of the congeners are expected to be highly bioaccumulative. MCCPs and LCCPs have been found in all types of environmental media far from their sources, as well as observed in indoor air and house dust, food, fish, human breast milk, and cow’s milk. The assessment will focus on MCCPs (C14-C17) and certain LCCPs (C18-C20) that have received the most international regulatory attention. Based on the screening assessments regarding persistence and bioaccumulation, this assessment will consider PBT aspects of MCCPs and LCCPs, primarily focusing on releases to the environment from the processing and use from metal working fluids and plastics/rubber (PVC) compounding. EPA anticipates issuing draft risk assessments for public review and comment as they are completed. At the conclusion of the review process, if

Dietary habits in adolescence and midlife and risk of breast cancer in older women

PubMed Central

Torfadottir, Johanna E.; Valdimarsdottir, Unnur A.; Adami, Hans-Olov; Aspelund, Thor; Tryggvadottir, Laufey; Thordardottir, Marianna; Birgisdottir, Bryndis E.; Harris, Tamara B.; Launer, Lenore J.; Gudnason, Vilmundur; Steingrimsdottir, Laufey

2018-01-01

Recent studies indicate that lifestyle factors in early life affect breast cancer risk. We therefore explored the association of high consumption of meat, milk, and whole grain products in adolescence and midlife, on breast cancer risk. We used data from the population based AGES-Reykjavik cohort (2002–2006), where 3,326 women with a mean age of 77 years (SD 6.0) participated. For food items and principal component derived dietary patterns we used Cox proportional models to calculate multivariate hazard ratios (HR) with 95% confidence intervals (95% CI). During a mean follow-up of 8.8 years, 97 women were diagnosed with breast cancer. For both adolescence and midlife, daily consumption of rye bread was positively associated with breast cancer (HR 1.7, 95% CI 1.1–2.6 and HR 1.8, 95% CI 1.1–2.9, respectively). In contrast, persistent high consumption of oatmeal was negatively associated with breast cancer (0.4, 95% CI 0.2–0.9). No association was found for other food items or dietary patterns that included rye bread. High rye bread consumption in adolescence and midlife may increase risk of late-life breast cancer whilst persistent consumption of oatmeal may reduce the risk. PMID:29847592

Pharmaceutical metabolites in the environment: analytical challenges and ecological risks.

PubMed

Celiz, Mary D; Tso, Jerry; Aga, Diana S

2009-12-01

The occurrence of human and veterinary pharmaceuticals in the environment has been a subject of concern for the past decade because many of these emerging contaminants have been shown to persist in soil and water. Although recent studies indicate that pharmaceutical contaminants can pose long-term ecological risks, many of the investigations regarding risk assessment have only considered the ecotoxicity of the parent drug, with very little attention given to the potential contributions that metabolites may have. The scarcity of available environmental data on the human metabolites excreted into the environment or the microbial metabolites formed during environmental biodegradation of pharmaceutical residues can be attributed to the difficulty in analyzing trace amounts of previously unknown compounds in complex sample matrices. However, with the advent of highly sensitive and powerful analytical instrumentations that have become available commercially, it is likely that an increased number of pharmaceutical metabolites will be identified and included in environmental risk assessment. The present study will present a critical review of available literature on pharmaceutical metabolites, primarily focusing on their analysis and toxicological significance. It is also intended to provide an overview on the recent advances in analytical tools and strategies to facilitate metabolite identification in environmental samples. This review aims to provide insight on what future directions might be taken to help scientists in this challenging task of enhancing the available data on the fate, behavior, and ecotoxicity of pharmaceutical metabolites in the environment.

Risk Factors for Bartonella species Infection in Blood Donors from Southeast Brazil.

PubMed

Diniz, Pedro Paulo Vissotto de Paiva; Velho, Paulo Eduardo Neves Ferreira; Pitassi, Luiza Helena Urso; Drummond, Marina Rovani; Lania, Bruno Grosselli; Barjas-Castro, Maria Lourdes; Sowy, Stanley; Breitschwerdt, Edward B; Scorpio, Diana Gerardi

2016-03-01

Bacteria from the genus Bartonella are emerging blood-borne bacteria, capable of causing long-lasting infection in marine and terrestrial mammals, including humans. Bartonella are generally well adapted to their main host, causing persistent infection without clinical manifestation. However, these organisms may cause severe disease in natural or accidental hosts. In humans, Bartonella species have been detected from sick patients presented with diverse disease manifestations, including cat scratch disease, trench fever, bacillary angiomatosis, endocarditis, polyarthritis, or granulomatous inflammatory disease. However, with the advances in diagnostic methods, subclinical bloodstream infection in humans has been reported, with the potential for transmission through blood transfusion been recently investigated by our group. The objective of this study was to determine the risk factors associated with Bartonella species infection in asymptomatic blood donors presented at a major blood bank in Southeastern Brazil. Five hundred blood donors were randomly enrolled and tested for Bartonella species infection by specialized blood cultured coupled with high-sensitive PCR assays. Epidemiological questionnaires were designed to cover major potential risk factors, such as age, gender, ethnicity, contact with companion animals, livestock, or wild animals, bites from insects or animal, economical status, among other factors. Based on multivariate logistic regression, bloodstream infection with B. henselae or B. clarridgeiae was associated with cat contact (adjusted OR: 3.4, 95% CI: 1.1-9.6) or history of tick bite (adjusted OR: 3.7, 95% CI: 1.3-13.4). These risk factors should be considered during donor screening, as bacteremia by these Bartonella species may not be detected by traditional laboratory screening methods, and it may be transmitted by blood transfusion.

Turtle-Associated Salmonellosis, United States, 2006–2014

PubMed Central

Tauxe, Robert V.; Behravesh, Casey Barton

2016-01-01

During 2006–2014, a total of 15 multistate outbreaks of turtle-associated salmonellosis in humans were reported in the United States. Exposure to small pet turtles has long been recognized as a source of human salmonellosis. The risk to public health has persisted and may be increasing. Turtles are a popular reptilian pet among children, and numerous risky behaviors for the zoonotic transmission of Salmonella bacteria to children have been reported in recent outbreaks. Despite a long-standing federal ban against the sale and distribution of turtles <4 in (<10.16 cm) long, these small reptiles can be readily acquired through multiple venues and continue to be the main source of turtle-associated salmonellosis in children. Enhanced efforts are needed to minimize the disease risk associated with small turtle exposure. Prevention will require novel partnerships and a comprehensive One Health approach involving human, animal, and environmental health. PMID:27315584

Turtle-Associated Salmonellosis, United States, 2006-2014.

PubMed

Bosch, Stacey; Tauxe, Robert V; Behravesh, Casey Barton

2016-07-01

During 2006-2014, a total of 15 multistate outbreaks of turtle-associated salmonellosis in humans were reported in the United States. Exposure to small pet turtles has long been recognized as a source of human salmonellosis. The risk to public health has persisted and may be increasing. Turtles are a popular reptilian pet among children, and numerous risky behaviors for the zoonotic transmission of Salmonella bacteria to children have been reported in recent outbreaks. Despite a long-standing federal ban against the sale and distribution of turtles <4 in (<10.16 cm) long, these small reptiles can be readily acquired through multiple venues and continue to be the main source of turtle-associated salmonellosis in children. Enhanced efforts are needed to minimize the disease risk associated with small turtle exposure. Prevention will require novel partnerships and a comprehensive One Health approach involving human, animal, and environmental health.

Reminders of cancer risk and pain catastrophizing: relationships with cancer worry and perceived risk in women with a first-degree relative with breast cancer.

PubMed

Whitney, Colette A; Dorfman, Caroline S; Shelby, Rebecca A; Keefe, Francis J; Gandhi, Vicky; Somers, Tamara J

2018-04-20

First-degree relatives of women with breast cancer may experience increased worry or perceived risk when faced with reminders of their own cancer risk. Worry and risk reminders may include physical symptoms (e.g., persistent breast pain) and caregiving experiences. Women who engage in pain catastrophizing may be particularly likely to experience increased distress when risk reminders are present. We examined the degree to which persistent breast pain and experience as a cancer caregiver were related to cancer worry and perceived risk in first-degree relatives of women with breast cancer (N = 85) and how catastrophic thoughts about breast pain could impact these relationships. There was a significant interaction between persistent breast pain and pain catastrophizing in predicting cancer worry (p = .03); among women who engaged in pain catastrophizing, cancer worry remained high even in the absence of breast pain. Pain catastrophizing also moderated the relationships between caregiving involvement and cancer worry (p = .003) and perceived risk (p = .03). As the degree of caregiving responsibility increased, cancer worry and perceived risk increased for women who engaged in pain catastrophizing; levels of cancer worry and perceived risk remained low and stable for women who did not engage in pain catastrophizing regardless of caregiving experience. The results suggest that first-degree relatives of breast cancer survivors who engage in pain catastrophizing may experience greater cancer worry and perceived risk and may benefit from interventions aimed at reducing catastrophic thoughts about pain.

THE POLITICS OF RISK AND EU GOVERNANCE OF HUMAN MATERIAL

PubMed Central

Farrel, Anne-Maree

2012-01-01

This paper examines the politics of EU risk governance in relation to human material. It is argued that the political context has informed the way in which risks in relation to various types of human material have come to be defined as policy problems at EU level. In turn, this has influenced the design and/or persistence of institutional arrangements to manage such problems. It is further argued that this political context has resulted in a significant level of disconnection in risk governance in the area. This has happened in two ways. First, there has been a growing level of disconnection between institutional and stakeholder demands for a more expansive approach to risk governance in the area and the narrowly-circumscribed competence under Article 152(4)(a) EC, which permits the adoption of risk regulation regimes that set minimum standards of quality and safety in relation to blood, tissue/cells and organs. Second, it has led to the development of institutional arrangements that promote a bifurcated approach to risk governance, specifically in relation to blood and tissues/cells. Although a hybrid of traditional and new governance mechanisms have been employed to address this problem of disconnection, this has nevertheless added a further layer to already complex institutional arrangements for risk governance in the area. It is suggested that a more integrated approach to EU risk governance in relation to human material is needed. Implementing such an approach would contribute to greater clarity, transparency and accountability in decision-making processes, and this could enhance public trust in what is a politically-sensitive area of governance at EU level. PMID:23326180

Distribution and ecological risk of organic pollutants in the sediments and seafood of Yangtze Estuary and Hangzhou Bay, East China Sea.

PubMed

Adeleye, Adedayo O; Jin, Haiyan; Di, Yanan; Li, Donghao; Chen, Jianfang; Ye, Ying

2016-01-15

A wide variety of persistent organic pollutants (POPs) in the surface marine sediments and seafood from four geographic areas of the East China Sea were investigated. The POP concentrations were analyzed and their possible ecotoxicological risks assessed. The total concentrations of hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) in the sediments were found to be ND-22.40, ND-5.10, 32.10-171.70, and 0.60-63.00 ng/g dry weight (dw), respectively. Low-chlorinated biphenyl congeners and HCHs were predominantly found at the Hangzhou Bay and Yangtze River areas. The sediment ecotoxicological risk was assessed, indicating the toxic effect of PCBs and DDTs on benthic organisms. In marine organisms of economic importance, the concentration of total PAHs, PCBs, and organochlorine pesticides (OCPs) ranged from 43.20 to 291.20, 2.60 to 96.20, and 12.70 to 235.20 μg/kg dw, respectively. The bioaccumulation in marine organisms did not pose a significant health risk to consumers. As indicated by the POP residues in both marine sediments and organisms, POPs were persistent over time, posing a long-term risk to the local ecosystem and human health via the food chain. Copyright © 2015 Elsevier B.V. All rights reserved.

[Epidemic of Staphylococcus aureus nosocomial infections resistant to methicillin in a maternity ward].

PubMed

Le Coq, M; Simon, I; Sire, C; Tissot-Guerraz, F; Fournier, L; Aho, S; Noblot, G; Reverdy, M E; Françoise, M

2001-02-01

Methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections frequently occur in the hospital environment, but their incidence is less often observed in neonates. In the present investigation, seventeen cases were recorded over a nine-week period (two cases per week). Pulsed field gradient gel electrophoresis confirmed the clonal character of the strain. The hypothesis of manually-transmitted infection due to contamination from multiple sources was reinforced by the fact the epidemic persisted in spite of the elimination of the main human infectious source and an absence of risk factors determined by the case-control study. The role of environmental factors in the persistence of this outbreak of MRSA infection has been considered.

Extreme weather events and infectious disease outbreaks.

PubMed

McMichael, Anthony J

2015-01-01

Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental conditions of extreme weather events. This review article examines infectious disease risks associated with extreme weather events; it draws on recent experiences including Hurricane Katrina in 2005 and the 2010 Pakistan mega-floods, and historical examples from previous centuries of epidemics and 'pestilence' associated with extreme weather disasters and climatic changes. A fuller understanding of climatic change, the precursors and triggers of extreme weather events and health consequences is needed in order to anticipate and respond to the infectious disease risks associated with human-driven climate change. Post-event risks to human health can be constrained, nonetheless, by reducing background rates of persistent infection, preparatory action such as coordinated disease surveillance and vaccination coverage, and strengthened disaster response. In the face of changing climate and weather conditions, it is critically important to think in ecological terms about the determinants of health, disease and death in human populations.

DDT Exposure in Utero and Breast Cancer.

PubMed

Cohn, Barbara A; La Merrill, Michele; Krigbaum, Nickilou Y; Yeh, Gregory; Park, June-Soo; Zimmermann, Lauren; Cirillo, Piera M

2015-08-01

Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. In utero exposure to DDT is associated with an increased risk of breast cancer. This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. Maternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.

Disparity in the Persistence of High-Risk Human Papillomavirus Genotypes Between African American and European American Women of College Age

PubMed Central

Banister, Carolyn E.; Messersmith, Amy R.; Cai, Bo; Spiryda, Lisa B.; Glover, Saundra H.; Pirisi, Lucia; Creek, Kim E.

2015-01-01

Background. Cervical cancer incidence and mortality rates are higher in African Americans than in European Americans (white, non-Hispanic of European ancestry). The reasons for this disparity are not known. Methods. We recruited a population-based longitudinal cohort of 326 European American and 113 African American female college freshmen in Columbia, South Carolina, to compare clearance of high-risk human papillomavirus (HR-HPV) infection between ethnicities. HPV testing and typing from samples obtained for Papanicolaou testing occurred every 6 months. Results. African American participants had an increased risk of testing positive for HR-HPV, compared with European American participants, but the frequency of incident HPV infection was the same in African American and European American women. Thus, exposure to HPV could not explain the higher rate of HPV positivity among African American women. The time required for 50% of participants to clear HR-HPV infection was 601 days for African American women (n = 63) and 316 days for European American women (n = 178; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08–2.53). African American women were more likely than European American women to have an abnormal result of a Papanicolaou test (OR, 1.58; 95% CI, 1.05–2.39). Conclusions. We propose that the longer time to clearance of HR-HPV among African American women leads to increased rates of abnormal results of Papanicolaou tests and contributes to the increased rates of cervical cancer observed in African American women. PMID:25028692

Human papillomavirus-related content in state and tribal comprehensive cancer control plans.

PubMed

Steele, C Brooke; Thomas, Christopher N; Richardson, Lisa C

2008-01-01

Oncogenic types of the human papillomavirus (HPV) are firmly established as etiological agents for most premalignant and malignant epithelial lesions of the cervical mucosa. Genital infection with HPV is the most common sexually transmitted infection (STI) in the United States. Although most women infected with the virus become HPV negative within 2 years, women with persistent high-risk HPV infections are at greatest risk for developing cervical cancer. Since the development of the Papanicolau (Pap) test more than 60 years ago to screen for cervical cancer, technological advances have occurred in cervical cytology screening and HPV vaccine research. For example, in 2001, high-risk HPV DNA testing was recommended for the management of women whose Pap smears (collected by a liquid-based method) reveal atypical squamous cells of undetermined significance. In 2006, the Food and Drug Administration licensed a quadrivalent HPV vaccine for females aged 9-26 years to prevent cervical cancer, precancerous lesions, and genital warts associated with HPV types in the vaccine. New and emerging technologies in cancer diagnosis, management, and prevention are often addressed in comprehensive cancer control (CCC) plans developed by states, tribes, and territories. CCC is a collaborative process through which a community and its partners pool resources to reduce the burden of cancer. To assess whether CCC plans include HPV-related content, particularly regarding cervical cancer screening and prevention, we reviewed the most current plans available between October 2006 and January 2007 on an interactive Internet site for CCC programs (n = 53). This paper describes the contexts in which HPV-related content occurs in the plans.

Pharmaceuticals and personal care products (PPCPs): a review on environmental contamination in China.

PubMed

Liu, Jin-Lin; Wong, Ming-Hung

2013-09-01

Pharmaceuticals and personal care products (PPCPs) which contain diverse organic groups, such as antibiotics, hormones, antimicrobial agents, synthetic musks, etc., have raised significant concerns in recently years for their persistent input and potential threat to ecological environment and human health. China is a large country with high production and consumption of PPCPs for its economic development and population growth in recent years. This may result in PPCP contamination in different environmental media of China. This review summarizes the current contamination status of different environment media, including sewage, surface water, sludge, sediments, soil, and wild animals, in China by PPCPs. The human body burden and adverse effects derived from PPCPs are also evaluated. Based on this review, it has been concluded that more contamination information of aquatic environment and wildlife as well as human body burden of PPCPs in different areas of China is urgent. Studies about their environmental behavior and control technologies need to be conducted, and acute and chronic toxicities of different PPCP groups should be investigated for assessing their potential ecological and health risks. © 2013.

Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.

PubMed

Blitz, Sandra; Baxter, Joanna; Raboud, Janet; Walmsley, Sharon; Rachlis, Anita; Smaill, Fiona; Ferenczy, Alex; Coutlée, François; Hankins, Catherine; Money, Deborah

2013-08-01

The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.

ESR1 Promoter Hypermethylation Does Not Predict Atypia in RPFNA nor Persistent Atypia after 12 Months Tamoxifen Chemoprevention

PubMed Central

Baker, Joseph C.; Ostrander, Julie H.; Lem, Siya; Broadwater, Gloria; Bean, Gregory R.; D'Amato, Nicholas C.; Goldenberg, Vanessa K.; Rowell, Craig; Ibarra-Drendall, Catherine; Grant, Tracey; Pilie, Patrick G.; Vasilatos, Shauna N.; Troch, Michelle M.; Scott, Victoria; Wilke, Lee G.; Paisie, Carolyn; Rabiner, Sarah M.; Torres-Hernandez, Alejandro; Zalles, Carola M.; Seewaldt, Victoria L.

2009-01-01

Purpose Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention. Experimental Design Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls. Results We observed a statistically significant decrease in the Masood score of women on tamoxifen chemoprevention for 12 months compared with control women. This was a significant interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor low ER expression predicted persistent atypia in Random Periareolar Fine Needle Aspiration after 12 months tamoxifen prevention. Conclusions Results from this single institution pilot study provide evidence that, unlike for invasive breast cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable marker of tamoxifen-resistant atypia. PMID:18708376

Perception of blood transfusion risk.

PubMed

Lee, David

2006-04-01

Perceptions of risk ultimately drive the responses of individuals and society to risk issues, and transfusion risk is no exception. Surveys of lay people over the past decade indicate that public concern about transfusion safety has remained prevalent, dominated by the ongoing fear of contracting HIV infection. Such perceptions persist despite the acknowledgment that blood transfusion is safer now than in years past. Judgements by the lay public that may, at first glance, seem irrational can often be understood when the heuristics, biases, and models of human judgements of risk are considered. Risk perception research suggests that how lay people perceive risk has less to do with the unidimensional view of risk as a probabilistic expression and more to do with a complex multidimensional construct in which affect, reason, worldviews, trust, and other factors are intertwined. This review summarizes some of the principles of risk perception as applicable to transfusion medicine.

The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity.

PubMed

Wardenaar, K J; van Loo, H M; Cai, T; Fava, M; Gruber, M J; Li, J; de Jonge, P; Nierenberg, A A; Petukhova, M V; Rose, S; Sampson, N A; Schoevers, R A; Wilcox, M A; Alonso, J; Bromet, E J; Bunting, B; Florescu, S E; Fukao, A; Gureje, O; Hu, C; Huang, Y Q; Karam, A N; Levinson, D; Medina Mora, M E; Posada-Villa, J; Scott, K M; Taib, N I; Viana, M C; Xavier, M; Zarkov, Z; Kessler, R C

2014-11-01

Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these distinctions can be refined by added information about co-morbid conditions. The current report presents results on this question. Data came from 8261 respondents with lifetime DSM-IV MDD in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Outcomes included four retrospectively reported measures of persistence/severity of course (years in episode; years in chronic episodes; hospitalization for MDD; disability due to MDD). Machine learning methods (regression tree analysis; lasso, ridge and elastic net penalized regression) followed by k-means cluster analysis were used to augment previously detected subtypes with information about prior co-morbidity to predict these outcomes. Predicted values were strongly correlated across outcomes. Cluster analysis of predicted values found three clusters with consistently high, intermediate or low values. The high-risk cluster (32.4% of cases) accounted for 56.6-72.9% of high persistence, high chronicity, hospitalization and disability. This high-risk cluster had both higher sensitivity and likelihood ratio positive (LR+; relative proportions of cases in the high-risk cluster versus other clusters having the adverse outcomes) than in a parallel analysis that excluded measures of co-morbidity as predictors. Although the results using the retrospective data reported here suggest that useful MDD subtyping distinctions can be made with machine learning and clustering across multiple indicators of illness persistence/severity, replication with prospective data is needed to confirm this preliminary conclusion.

Associations between cumulative neighborhood deprivation, long-term mobility trajectories, and gestational weight gain.

PubMed

Headen, Irene; Mujahid, Mahasin; Deardorff, Julianna; Rehkopf, David H; Abrams, Barbara

2018-06-05

Existing research on neighborhood environment and gestational weight gain (GWG) focuses on point-in-time measures of neighborhood context. This precludes understanding how long-term exposure to adverse neighborhood environments influences GWG. We estimated associations between average exposure to and trajectories of long-term neighborhood socioeconomic deprivation and risk of inadequate or excessive GWG. Using data from 5690 full-term, singleton pregnancies in the 1979 National Longitudinal Survey of Youth, we estimated associations between cumulative deprivation and GWG, overall and by race/ethnicity, controlling for individual and residential covariates. A one standard deviation unit (8-point) increase in neighborhood deprivation increased risk of inadequate GWG (Relative Risk (RR): 1.08; 95% Confidence Interval (CI): 1.00-1.16) for all women and excessive GWG (RR: 1.11; 95% CI 1.02-1.21) for white women. Persistent low deprivation (RR: 0.78; 95% CI: 0.64-0.94) and upward mobility (RR: 0.76; 95% CI: 0.61-0.96), compared to persistent high deprivation, reduced risk of inadequate GWG. Persistent low deprivation also reduced risk of excessive GWG (RR: 0.84; 95% CI: 0.71-0.98). Long-term neighborhood deprivation contributes to patterns of GWG over women's life course. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

PubMed

Panagopoulou, Maria; Lambropoulou, Maria; Balgkouranidou, Ioanna; Nena, Evangelia; Karaglani, Makrina; Nicolaidou, Christina; Asimaki, Anthi; Konstantinidis, Theocharis; Constantinidis, Theodoros C; Kolios, George; Kakolyris, Stylianos; Agorastos, Theodoros; Chatzaki, Ekaterini

2017-04-01

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

Free-grazing Ducks and Highly Pathogenic Avian Influenza, Thailand

PubMed Central

Chaitaweesub, Prasit; Parakamawongsa, Tippawon; Premashthira, Sith; Tiensin, Thanawat; Kalpravidh, Wantanee; Wagner, Hans; Slingenbergh, Jan

2006-01-01

Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI outbreaks in relation to poultry, land use, and other anthropogenic variables from the start of the second epidemic wave (July 2004–May 2005). Results demonstrate a strong association between H5N1 virus in Thailand and abundance of free-grazing ducks and, to a lesser extent, native chickens, cocks, wetlands, and humans. Wetlands used for double-crop rice production, where free-grazing duck feed year round in rice paddies, appear to be a critical factor in HPAI persistence and spread. This finding could be important for other duck-producing regions in eastern and southeastern Asian countries affected by HPAI. PMID:16494747

Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.

PubMed

Marsh, Elizabeth K; Delury, Craig P; Davies, Nicholas J; Weston, Christopher J; Miah, Mohammed A L; Banks, Lawrence; Parish, Joanna L; Higgs, Martin R; Roberts, Sally

2017-03-21

The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification.

Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus, Guangdong, China

PubMed Central

Wu, Jie; Lu, Jing; Faria, Nuno R.; Zeng, Xianqiao; Song, Yingchao; Zou, Lirong; Yi, Lina; Liang, Lijun; Ni, Hanzhong; Kang, Min; Zhang, Xin; Huang, Guofeng; Zhong, Haojie; Bowden, Thomas A.; Raghwani, Jayna; He, Jianfeng; He, Xiang; Lin, Jinyan; Koopmans, Marion; Pybus, Oliver G.

2016-01-01

Since March 2013, three waves of human infection with avian influenza A(H7N9) virus have been detected in China. To investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in Guangdong during 2013–2015. We observed a geographic shift of human A(H7N9) infections from the second to the third waves. Live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated that the third-wave outbreaks in central Guangdong most likely resulted from local virus persistence rather than introduction from elsewhere. Although the number of clinical cases in humans declined by 35% from the second to the third waves, the genetic diversity of third-wave viruses in Guangdong increased. Our results highlight the epidemic risk to a region reporting comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry market interventions cannot completely halt A(H7N9) virus persistence and dissemination. PMID:27869613

Risk factors predicting onset and persistence of subthreshold expression of bipolar psychopathology among youth from the community.

PubMed

Tijssen, M J A; Van Os, J; Wittchen, H U; Lieb, R; Beesdo, K; Wichers, Marieke

2010-09-01

To examine factors increasing the risk for onset and persistence of subthreshold mania and depression. In a prospective cohort community study, the association between risk factors [a family history of mood disorders, trauma, substance use, attention-deficit/hyperactivity disorder (ADHD) and temperamental/personality traits] and onset of manic/depressive symptoms was determined in 705 adolescents. The interaction between baseline risk factors and baseline symptoms in predicting 8-year follow-up symptoms was used to model the impact of risk factors on persistence. Onset of manic symptoms was associated with cannabis use and novelty seeking (NS), but NS predicted a transitory course. Onset of depressive symptoms was associated with a family history of depression. ADHD and harm avoidance (HA) were associated with persistence of depressive symptoms, while trauma and a family history of depression predicted a transitory course. Different risk factors may operate during onset and persistence of subthreshold mania and depression. The differential associations found for mania and depression dimensions suggest partly different underlying mechanisms.

How to tackle the problem early? The role of education in the prevention of obesity.

PubMed

Dietz, W

1999-05-01

The major issues that confront the clinician in relation to childhood obesity are identifying children at risk, deciding the goal and focus of therapy, and determining how to maintain weight loss. The severity of obesity and the age at which it is present appear to be significant determinants of whether childhood obesity will persist into adulthood. At any age, severe obesity is more likely to persist, and obesity present in adolescents is much more likely to persist than obesity in young children. If a child has obese parents, the risk that their obesity will persist to adulthood increases, though the magnitude of that risk varies with the age of the child. The goals of therapy depend on the child's age and the severity of obesity-related complications. Assessment of the family's readiness to change represents the first focus of therapy. A reduction in time spent watching television, coupled with family involvement and a diet that aims to reduce or eliminate high caloric density foods is the best approach in most cases. Children or adolescents who have an emergent complication of obesity are candidates for aggressive weight reduction such as the protein modified fast. More aggressive therapies, such as drug therapy or gastric bypass surgery, must be considered as experimental in children and adolescents.

[Persistent, excessive crying in 5-month-old infants and the pre-, peri- and postnatal adversities of their mothers in a high-risk sample].

PubMed

Sidor, Anna; Thiel-Bonney, Consolata; Kunz, Elisabeth; Eickhorst, Andreas; Cierpka, Manfred

2012-07-01

To investigate the relationship between persistent, excessive crying in 5-month-old infants and the pre- and perinatal adversities as well as postpartal mood of their mothers. A sample of 300 mother-child dyads was examined at infants' age of 18.5 weeks. All mothers exhibited psychosocial risks such as poverty, lack of social support, being underage, drug abuse or mental disorders. Excessive crying was assessed by the Wessel's «rule of threes». Pre-, peri- and postnatal problems were measured by self-report questionnaires. Multivariate data analysis revealed an increased risk for social adversities during pregnancy (OR = 17.66) and unwanted pregnancy (OR = 13.77). For the postnatal period persistent crying was associated with a higher rate of maternal postpartum depressive symptoms, maternal stress, dysfunctional mother-child interactions, perception of the infant as being «difficult» as well as bonding problems. The results point to the influence of prenatal stress in mothers and a primarily unwanted pregnancy on infants' persistent crying. An increased need for support is suggested in cases of considerably reduced well-being of the mother or bonding problems. The combined effect of prenatal variables and relationship variables influences the occurrence and perpetuation of early regulation problems.

SOX2 as a New Regulator of HPV16 Transcription.

PubMed

Martínez-Ramírez, Imelda; Del-Castillo-Falconi, Víctor; Mitre-Aguilar, Irma B; Amador-Molina, Alfredo; Carrillo-García, Adela; Langley, Elizabeth; Zentella-Dehesa, Alejandro; Soto-Reyes, Ernesto; García-Carrancá, Alejandro; Herrera, Luis A; Lizano, Marcela

2017-07-05

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.

Development of risk reduction behavioral counseling for Ebola virus disease survivors enrolled in the Sierra Leone Ebola Virus Persistence Study, 2015-2016.

PubMed

Abad, Neetu; Malik, Tasneem; Ariyarajah, Archchun; Ongpin, Patricia; Hogben, Matthew; McDonald, Suzanna L R; Marrinan, Jaclyn; Massaquoi, Thomas; Thorson, Anna; Ervin, Elizabeth; Bernstein, Kyle; Ross, Christine; Liu, William J; Kroeger, Karen; Durski, Kara N; Broutet, Nathalie; Knust, Barbara; Deen, Gibrilla F

2017-09-01

During the 2014-2016 West Africa Ebola Virus Disease (EVD) epidemic, the public health community had concerns that sexual transmission of the Ebola virus (EBOV) from EVD survivors was a risk, due to EBOV persistence in body fluids of EVD survivors, particularly semen. The Sierra Leone Ebola Virus Persistence Study was initiated to investigate this risk by assessing EBOV persistence in numerous body fluids of EVD survivors and providing risk reduction counseling based on test results for semen, vaginal fluid, menstrual blood, urine, rectal fluid, sweat, tears, saliva, and breast milk. This publication describes implementation of the counseling protocol and the key lessons learned. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol was developed from a framework used to prevent transmission of HIV and other sexually transmitted infections. The framework helped to identify barriers to risk reduction and facilitated the development of a personalized risk-reduction plan, particularly around condom use and abstinence. Pre-test and post-test counseling sessions included risk reduction guidance, and post-test counseling was based on the participants' individual test results. The behavioral counseling protocol enabled study staff to translate the study's body fluid test results into individualized information for study participants. The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol provided guidance to mitigate the risk of EBOV transmission from EVD survivors. It has since been shared with and adapted by other EVD survivor body fluid testing programs and studies in Ebola-affected countries.

Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

PubMed

Margulescu, Andrei D; Mont, Lluis

2017-08-01

Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

The epidemiology of depression across cultures

PubMed Central

Kessler, Ronald C.; Bromet, Evelyn J.

2014-01-01

Epidemiological data are reviewed on the prevalence, course, socio-demographic correlates, and societal costs of major depression throughout the world. Major depression is estimated in these surveys to be a commonly-occurring disorder. Although estimates of lifetime prevalence and course vary substantially across countries for reasons that could involve both substantive and methodological processes, the cross-national data are clear in documenting meaningful lifetime prevalence with wide variation in age-of-onset and high risk of lifelong chronic-recurrent persistence. A number of socio-demographic correlates of major depression are found consistently across countries and cross-national data also document associations with numerous adverse outcomes, including difficulties in role transitions (e.g., low education, high teen child-bearing, marital disruption, unstable employment), reduced role functioning (e.g., low marital quality, low work performance, low earnings), elevated risk of onset, persistence, and severity of a wide range of secondary disorders, and increased risk of early mortality due to physical disorders and suicide. PMID:23514317

Fragmentation and thermal risks from climate change interact to affect persistence of native trout in the Colorado River basin.

PubMed

Roberts, James J; Fausch, Kurt D; Peterson, Douglas P; Hooten, Mevin B

2013-05-01

Impending changes in climate will interact with other stressors to threaten aquatic ecosystems and their biota. Native Colorado River cutthroat trout (CRCT; Oncorhynchus clarkii pleuriticus) are now relegated to 309 isolated high-elevation (>1700 m) headwater stream fragments in the Upper Colorado River Basin, owing to past nonnative trout invasions and habitat loss. Predicted changes in climate (i.e., temperature and precipitation) and resulting changes in stochastic physical disturbances (i.e., wildfire, debris flow, and channel drying and freezing) could further threaten the remaining CRCT populations. We developed an empirical model to predict stream temperatures at the fragment scale from downscaled climate projections along with geomorphic and landscape variables. We coupled these spatially explicit predictions of stream temperature with a Bayesian Network (BN) model that integrates stochastic risks from fragmentation to project persistence of CRCT populations across the upper Colorado River basin to 2040 and 2080. Overall, none of the populations are at risk from acute mortality resulting from high temperatures during the warmest summer period. In contrast, only 37% of populations have a ≥90% chance of persistence for 70 years (similar to the typical benchmark for conservation), primarily owing to fragmentation. Populations in short stream fragments <7 km long, and those at the lowest elevations, are at the highest risk of extirpation. Therefore, interactions of stochastic disturbances with fragmentation are projected to be greater threats than warming for CRCT populations. The reason for this paradox is that past nonnative trout invasions and habitat loss have restricted most CRCT populations to high-elevation stream fragments that are buffered from the potential consequences of warming, but at risk of extirpation from stochastic events. The greatest conservation need is for management to increase fragment lengths to forestall these risks. © 2013 Blackwell Publishing Ltd.

Fragmentation and thermal risks from climate change interact to affect persistence of native trout in the Colorado River basin

USGS Publications Warehouse

Roberts, James J.; Fausch, Kurt D.; Peterson, Douglas P.; Hooten, Mevin B.

2013-01-01

Impending changes in climate will interact with other stressors to threaten aquatic ecosystems and their biota. Native Colorado River cutthroat trout (CRCT; Oncorhynchus clarkii pleuriticus) are now relegated to 309 isolated high-elevation (>1700 m) headwater stream fragments in the Upper Colorado River Basin, owing to past nonnative trout invasions and habitat loss. Predicted changes in climate (i.e., temperature and precipitation) and resulting changes in stochastic physical disturbances (i.e., wildfire, debris flow, and channel drying and freezing) could further threaten the remaining CRCT populations. We developed an empirical model to predict stream temperatures at the fragment scale from downscaled climate projections along with geomorphic and landscape variables. We coupled these spatially explicit predictions of stream temperature with a Bayesian Network (BN) model that integrates stochastic risks from fragmentation to project persistence of CRCT populations across the upper Colorado River basin to 2040 and 2080. Overall, none of the populations are at risk from acute mortality resulting from high temperatures during the warmest summer period. In contrast, only 37% of populations have a greater than or equal to 90% chance of persistence for 70 years (similar to the typical benchmark for conservation), primarily owing to fragmentation. Populations in short stream fragments <7 km long, and those at the lowest elevations, are at the highest risk of extirpation. Therefore, interactions of stochastic disturbances with fragmentation are projected to be greater threats than warming for CRCT populations. The reason for this paradox is that past nonnative trout invasions and habitat loss have restricted most CRCT populations to high-elevation stream fragments that are buffered from the potential consequences of warming, but at risk of extirpation from stochastic events. The greatest conservation need is for management to increase fragment lengths to forestall these risks. 

Chemical contamination of green turtle (Chelonia mydas) eggs in peninsular Malaysia: implications for conservation and public health.

PubMed

van de Merwe, Jason P; Hodge, Mary; Olszowy, Henry A; Whittier, Joan M; Ibrahim, Kamarruddin; Lee, Shing Y

2009-09-01

Persistent organic pollutants (POPs)-such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)-and heavy metals have been reported in sea turtles at various stages of their life cycle. These chemicals can disrupt development and function of wildlife. Furthermore, in areas such as Peninsular Malaysia, where the human consumption of sea turtle eggs is prevalent, egg contamination may also have public health implications. In the present study we investigated conservation and human health risks associated with the chemical contamination of green turtle (Chelonia mydas) eggs in Peninsular Malaysia. Fifty-five C. mydas eggs were collected from markets in Peninsular Malaysia and analyzed for POPs and heavy metals. We conducted screening risk assessments (SRAs) and calculated the percent of acceptable daily intake (ADI) for POPs and metals to assess conservation and human health risks associated with egg contamination. C. mydas eggs were available in 9 of the 33 markets visited. These eggs came from seven nesting areas from as far away as Borneo Malaysia. SRAs indicated a significant risk to embryonic development associated with the observed arsenic concentrations. Furthermore, the concentrations of coplanar PCBs represented 3 300 times the ADI values set by the World Health Organization. The concentrations of POPs and heavy metals reported in C. mydas eggs from markets in Peninsular Malaysia pose considerable risks to sea turtle conservation and human health.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

PubMed

Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

2016-02-01

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults.

PubMed

Ito, Kiyoaki; Yotsuyanagi, Hiroshi; Yatsuhashi, Hiroshi; Karino, Yoshiyasu; Takikawa, Yasuhiro; Saito, Takafumi; Arase, Yasuji; Imazeki, Fumio; Kurosaki, Masayuki; Umemura, Takeji; Ichida, Takafumi; Toyoda, Hidenori; Yoneda, Masashi; Mita, Eiji; Yamamoto, Kazuhide; Michitaka, Kojiro; Maeshiro, Tatsuji; Tanuma, Junko; Tanaka, Yasuhito; Sugiyama, Masaya; Murata, Kazumoto; Masaki, Naohiko; Mizokami, Masashi

2014-01-01

The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance. Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies. © 2013 by the American Association for the Study of Liver Diseases.

Strain- and Dose-Dependent Reduction of Toxoplasma gondii Burden in Pigs Is Associated with Interferon-Gamma Production by CD8+ Lymphocytes in a Heterologous Challenge Model

PubMed Central

Jennes, Malgorzata; De Craeye, Stéphane; Devriendt, Bert; Dierick, Katelijne; Dorny, Pierre; Cox, Eric

2017-01-01

Toxoplasma gondii is a worldwide prevalent parasite of humans and animals. The global infection burden exceeds yearly one million disability-adjusted life years (DALY's) in infected individuals. Therefore, effective preventive measures should be taken to decrease the risk of infection in humans. Although human toxoplasmosis is predominantly foodborne by ingestion of tissue cysts in meat from domestic animals such as pigs, the incidence risk is difficult to estimate due to the lack of screening of animals for infection and insights in location and persistence of the parasite in the tissues. Hence, experimental infections in pigs can provide more information on the risk for zoonosis based on the parasite burden in meat products intended for human consumption and on the immune responses induced by infection. In the present study, homo- and heterologous infection experiments with two distinct T. gondii strains (IPB-LR and IPB-Gangji) were performed. The humoral and cellular immune responses, the presence of viable parasites and the parasite load in edible meat samples were evaluated. In homologous infection experiments the parasite persistence was clearly strain-dependent and inversely correlated with the infection dose. The results strongly indicate a change in the amount of parasite DNA and viable cysts in porcine tissues over time. Heterologous challenge infections demonstrated that IPB-G strain could considerably reduce the parasite burden in the subsequent IPB-LR infection. A strong, however, not protective humoral response was observed against GRA7 and TLA antigens upon inoculation with both strains. The in vitro IFN-γ production by TLA-stimulated PBMCs was correlated with the infection dose and predominantly brought about by CD3+CD4−CD8αbright T-lymphocytes. The described adaptive cellular and humoral immune responses in pigs are in line with the induced or natural infections in mice and humans. Previous studies underscored the heterogeneity of T. gondii strains and the corresponding virulence factors. These findings suggest the potential of the IPB-G strain to elicit a partially protective immune response and to reduce the parasite burden upon a challenge infection. The IPB-G strain could be used as a promising tool in limiting the number of viable parasites in edible tissues and, hence, in lowering the risk for human toxoplasmosis. PMID:28642841

Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5-year depression trajectories using latent class growth analysis.

PubMed

Whitworth, S R; Bruce, D G; Starkstein, S E; Davis, W A; Davis, T M E; Skinner, T C; Bucks, R S

2017-08-01

To describe the long-term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories. A community-dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine-item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership. Three trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression - low-start; 7.3%); and gradually improving symptoms which later worsened (persistent depression - high-start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA 1c or self-monitoring of blood glucose. A subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow-up as part of routine Type 2 diabetes care. © 2017 Diabetes UK.

Ecological Forecasting of West Nile Virus Outbreaks in a High-Risk Area of the North-Central United States

NASA Astrophysics Data System (ADS)

Wimberly, M. C.; Merkord, C. L.; Kightlinger, L.; Vincent, G.; Hildreth, M. B.

2015-12-01

West Nile virus (WNV) is the most widespread and important mosquito-borne pathogen in North America. Since its emergence in the western hemisphere in 1999, human WNV disease has continued to exhibit recurrent outbreaks. Perplexingly, the incidence of this tropical disease has been highest in the cold-temperate climates of the Northern Great Plains (NGP). The spatial and temporal distributions of the vector mosquitoes and bird hosts, and consequently the risk of disease in humans, are strongly influenced by temperature, precipitation, vegetation, soils, and land use. We have utilized satellite remote sensing to map these environmental factors through time and develop models of disease risk. Outbreak years in South Dakota were preceded by warm winters, and WNV cases were most likely to occur during the hottest weeks of summer. Hot spots of persistent WNV transmission within the state were associated with rural land cover as well as patterns of physiography and climate. These models are currently being integrated into the South Dakota Mosquito Early Warning system (SDMIS), an automated WNV outbreak detection system that integrates remotely-sensed environmental indicators with vector abundance and infection data from a statewide mosquito surveillance network. The major goal of this effort is to leverage global environmental monitoring datasets to provide up-to-date, locally relevant information that can improve the effectiveness of mosquito control and disease prevention activities. This system was implemented for the first time during the summer of 2015. We will review the outcomes of this implementation, including the underlying influences of temperature on WNV risk, a preliminary statewide WNV risk map, and dynamic risk predictions made during the 2015 WNV season. Lessons learned as well as plans for future years will be discussed.

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

PubMed

Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

2018-04-03

Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

Guideline-conforming timing of invasive management in troponin-positive or high-risk ACS without persistent ST-segment elevation in German chest pain units. Urban university maximum care vs. rural regional primary care.

PubMed

Breuckmann, F; Remberg, F; Böse, D; Lichtenberg, M; Kümpers, P; Pavenstädt, H; Waltenberger, J; Fischer, D

2016-03-01

This study aimed to analyze guideline adherence in the timing of invasive management for myocardial infarction without persistent ST-segment elevation (NSTEMI) in two exemplary German centers, comparing an urban university maximum care facility and a rural regional primary care facility. All patients diagnosed as having NSTEMI during 2013 were retrospectively enrolled in two centers: (1) site I, a maximum care center in an urban university setting, and (b) site II, a primary care center in a rural regional care setting. Data acquisition included time intervals from admission to invasive management, risk criteria, rate of intervention, and medical therapy. The median time from admission to coronary angiography was 12.0 h (site I) or 17.5 h (site II; p = 0.17). Guideline-adherent timing was achieved in 88.1 % (site I) or 82.9 % (site II; p = 0.18) of cases. Intervention rates were high in both sites (site I-75.5 % vs. site II-75.3 %; p = 0.85). Adherence to recommendations of medical therapy was high and comparable between the two sites. In NSTEMI or high-risk acute coronary syndromes without persistent ST-segment elevation, guideline-adherent timing of invasive management was achieved in about 85 % of cases, and was comparable between urban maximum and rural primary care settings. Validation by the German Chest Pain Unit Registry including outcome analysis is required.

Critical evaluation of the cancer risk of dibromochloropropane (DBCP).

PubMed

Clark, Heather A; Snedeker, Suzanne M

2005-01-01

Dibromochloropropane (1,2-dibromo-3-chloropropane, DBCP), a pesticide used widely for over 20 years to control nematodes on crops, turf and in nurseries, was banned by the United States Environmental Protection Agency (US EPA) in 1977 because of evidence of infertility in men and induction of a variety of tumors in laboratory animals. Despite the ban on the use of DBCP, this pesticide remains persistent in soil and continues to be detected as a groundwater contaminant in areas of past high use, in particular California's Central Valley. In this review, we present a critical evaluation of the available scientific literature on the potential for DBCP to affect cancer risk, including the results of animal cancer bioassays, human epidemiological studies and in vitro and in vivo genotoxicity studies. In addition, we provide updated information on DBCP chemistry and metabolism, production and past use, current regulations, its environmental fate, potential for human exposure and current remediation efforts. Results from long-term cancer bioassays in rodents show a statistically significant increase in the incidence of malignant and benign mammary gland tumors in female rats treated orally with DBCP compared to controls and some evidence of increased incidence of mammary fibroadenomas in DBCP low-dose treated female rats exposed by inhalation. Significantly increased incidence of tumors of the forestomach occurred in both sexes of rats and mice treated orally. Rats exposed to DBCP by inhalation showed significant increases in tumors of the tunica vaginalis in males; tumors of the pharynx and adrenal gland in females; and tumors of the tongue, nasal turbinate and nasal cavity in both sexes compared to controls. Male and female mice exposed to DBCP by inhalation experienced increased tumor incidence in the lungs and nasal cavity compared to controls. Significant increases in tumors of the lung and forestomach have also been reported in female mice treated by a dermal route. Although high mortality rates in both rat and mouse bioassays limited the ability to detect tumors late in life, the induction of a variety of tumors by multiple routes of exposure in two rodent species provides clear evidence of a DBCP tumorigenic response. In vitro, in vivo and human genotoxicity studies indicate that DBCP is capable of acting as a mutagen and clastogen. Few studies have been conducted to assess whether DBCP workplace or drinking water exposures affect cancer risk in humans. While case-control, cohort and ecological epidemiology studies have not found significant, positive associations between DBCP exposure and cancer in exposed populations, these studies have numerous limitations including small numbers of participants, a lack of control for confounding factors, lack of exposure information on DBCP and other chemicals and short follow-up times. Given the persistent nature of DBCP contamination in areas of past use, efforts should be made to continue remediation efforts and follow previously exposed populations for development of certain human cancers, including breast, ovarian, stomach, respiratory, oral and nasal cancers, among others.

Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal areas, Pakistan: evaluation for human and ecological risk assessment.

PubMed

Saddique, Umar; Muhammad, Said; Tariq, Mohsin; Zhang, Hua; Arif, Mohammad; Jadoon, Ishtiaq A K; Khattak, Nimat Ullah

2018-03-22

Potentially toxic elements (PTEs) contaminations in the soil ecosystem are considered as extremely hazardous due to toxicity, persistence and bioaccumulative nature. Therefore, this study was aimed to summarize the results of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan. Results were evaluated for the pollution quantification factors, including contamination factor (CF), pollution load index (PLI), ecological risk index (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35) values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations were used to calculate the human exposure for the risk assessment, including chronic or non-carcinogenic risks such as the hazard quotient (HQ) and carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI, HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the mining activities, weathering and erosion of mafic and ultramafic bedrocks hosting ophiolites. This study strongly recommends that best control measures need to be taken for soil PTEs with the intent to alleviate any continuing potential threat to the human health, property and environment, which otherwise could enter ecosystem and ultimately the living beings. Further studies are recommended to combat the soil PTEs concentrations and toxicity in the Tribal areas for a best picture of understanding the element effects on human, and environment can be achieved that will lead to a sustainable ecological harmony.

Serotonergic, Brain Volume and Attentional Correlates of Trait Anxiety in Primates

PubMed Central

Mikheenko, Yevheniia; Shiba, Yoshiro; Sawiak, Stephen; Braesicke, Katrin; Cockcroft, Gemma; Clarke, Hannah; Roberts, Angela C

2015-01-01

Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders. PMID:25586542

The role of TLRs in cervical cancer with HPV infection: a review

PubMed Central

Yang, Xiao; Cheng, Yanxiang; Li, Chunsheng

2017-01-01

The main cause of cervical cancer is persistent infection with high-risk human papilloma virus (HR-HPV), but not all human papilloma virus (HPV) infections lead to cervical cancer. The key factors that determine the outcome of HPV infection remain poorly understood, and how the host immune system protects against HPV infection is unclear. Toll-like receptors (TLRs) are a group of pattern recognition receptors present in the cytoplasm and cell membrane, and can specifically recognize pathogen-associated molecular patterns. As the key molecules of innate and acquired immunity, TLRs not only play important roles in the immune defense against infectious diseases, but also are involved in the occurrence and development of a variety of malignant tumors. In cervical cancer caused by HR-HPV infection, TLRs have been found to regulate the local immune microenvironment. The role of TLRs in HR-HPV infection and HPV-induced cervical cancer and its relationship with HPV vaccine are reviewed in this article. PMID:29263932

Utilisation of co-testing 
(human papillomavirus DNA testing and cervical cytology) after treatment of CIN: - a survey of GPs' awareness and knowledge.

PubMed

Munro, Aime; Codde, Jim; Semmens, James; Leung, Yee; Spilsbury, Katrina; Williams, Vincent; Steel, Nerida; Cohen, Paul; Pavicic, Heidi; Westoby, Vicki; O'Leary, Peter

2015-01-01

Patients have an increased risk of persistent/recurrent cervical disease if they received treatment for a high-grade squamous intraepithelial lesion (HSIL). Consequently, understanding whether co-testing (human papillomavirus [HPV] DNA testing and cervical cytology) is fully utilised by general practitioners (GPs) is paramount. After consultation with key stakeholders, an anonymous, self-completion questionnaire was developed and disseminated to GPs who had provided cervical cytology. Responses were received from 745 GPs (30.9% response rate). A significant number (34.3%) of GPs were unaware of the use of co-testing (HPV DNA testing and cervical cytology) for the management of patients after HSIL treatment. Additionally, the majority of GPs reported they did not 'always' receive a clear follow-up plan for patients after treatment of an HSIL. GPs require further support and education to ensure successful adoption of co-testing (HPV DNA testing and cervical cytology), specifically, for patients treated for an HSIL.

HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers.

PubMed

Di Domenico, Marina; Giovane, Giancarlo; Kouidhi, Soumaya; Iorio, Rosamaria; Romano, Maurizio; De Francesco, Francesco; Feola, Antonia; Siciliano, Camilla; Califano, Luigi; Giordano, Antonio

2017-03-31

Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

Changes in vaginal community state types reflect major shifts in the microbiome

PubMed Central

Brooks, J. Paul; Buck, Gregory A.; Chen, Guanhua; Diao, Liyang; Edwards, David J.; Fettweis, Jennifer M.; Huzurbazar, Snehalata; Rakitin, Alexander; Satten, Glen A.; Smirnova, Ekaterina; Waks, Zeev; Wright, Michelle L.; Yanover, Chen; Zhou, Yi-Hui

2017-01-01

ABSTRACT Background: Recent studies of various human microbiome habitats have revealed thousands of bacterial species and the existence of large variation in communities of microorganisms in the same habitats across individual human subjects. Previous efforts to summarize this diversity, notably in the human gut and vagina, have categorized microbiome profiles by clustering them into community state types (CSTs). The functional relevance of specific CSTs has not been established. Objective: We investigate whether CSTs can be used to assess dynamics in the microbiome. Design: We conduct a re-analysis of five sequencing-based microbiome surveys derived from vaginal samples with repeated measures. Results: We observe that detection of a CST transition is largely insensitive to choices in methods for normalization or clustering. We find that healthy subjects persist in a CST for two to three weeks or more on average, while those with evidence of dysbiosis tend to change more often. Changes in CST can be gradual or occur over less than one day. Upcoming CST changes and switches to high-risk CSTs can be predicted with high accuracy in certain scenarios. Finally, we observe that presence of Gardnerella vaginalis is a strong predictor of an upcoming CST change. Conclusion: Overall, our results show that the CST concept is useful for studying microbiome dynamics. PMID:28572753

Sensitization to pets is a major determinant of persistent asthma and new asthma onset in Sweden

PubMed Central

Uddenfeldt, Monica; Janson, Christer; Lampa, Erik

2013-01-01

Introduction Our knowledge about atopy as a longitudinal predictor of asthma is limited. The purpose of this study was to investigate the prognosis of asthma and risk factors for asthma onset, especially sensitization of specific allergens in a population sample. Material and methods A cohort responded to a respiratory questionnaire in 1990 and 2003. At baseline, 2,060 subjects who, in the screening questionnaire, reported respiratory symptoms and 482 controls were investigated with interviews, spirometry, and skin-prick test. A total of 721 asthmatics and 976 subjects without respiratory disease were clinically verified. At follow-up in 2003, 340 subjects with persistent asthma and 186 subjects with asthma remission were identified, while 76 subjects reported new asthma onset. Results Sensitization to pets and a high symptom score were significant determinants of persistent asthma (odds ratio (OR) 3.2 (95% CI 1.9–5.6) and 5.7 (2.5–13.3), respectively) and onset of asthma (OR 2.6 (1.1–6.0), and 1.7 (1.2–2.3)). A high self-reported responsiveness to airway irritants (OR 1.6 (1.1–2.2)), and more asthma medications (OR 2.0 (1.3–2.9)) were additional indicators of persistent asthma at the follow-up. Belonging to the older age group decreased the risk both of having persistent asthma and asthma onset. Discussion Asthmatics sensitized to pets have a more severe outcome than asthmatics not sensitized to pets. Sensitization to pets was also a strong predictor for onset of asthma. Special attention should be given to asthmatics who report having severe symptoms and problems with airway irritants as such patients are more likely to have persistent problems. PMID:23339512

Human papilloma virus correlates of high grade cervical dysplasia in HIV-infected women in Mombasa, Kenya: a cross-sectional analysis.

PubMed

Menon, Sonia; Luchters, Stanley; Rossi, Rodolfo; Callens, Steven; Kishor, Mandaliya; Bogers, Johannes; Vanden Broeck, Davy

2018-03-27

Women living with HIV are at increased risk to be co-infected with HPV, persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR HPV viral load, which make them more at risk for cervical cancer. Despite their inherent vulnerability, there is a scarcity of data on potential high risk (pHR) and HR HPV genotypes in HIV- infected women with cervical dysplasia and HPV-type specific viral load in this population in Sub Saharan Africa. The aim of this analysis of HIV-infected women was to explore the virological correlates of high-grade cervical dysplasia (CIN 2+) in HIV-infected women, thereby profiling HPV genotypes. This analysis assesses baseline data obtained from a cohort study of 74 HIV-infected women with abnormal cytology attending a Comprehensive Care Centre for patients with HIV infection in Mombasa, Kenya. Quantitative real-time PCR was used for HPV typing and viral load. CIN 2 was observed in 16% (12/74) of women, CIN 3 in 23% (17/74), and, invasive cervical carcinoma (ICC) in 1% (1/74) of women. In women with CIN 3+, HPV 16 (44%), HPV 56 (33%), HPV 33 and 53 (HPV 53 (28%) were the most prevalent genotypes. HPV 53 was observed as a stand-alone HPV in one woman with ICC. A multivariate logistic regression adjusting for age, CD4 count and HPV co-infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted odds ratio [aOR]:4.9; p = 0.05; 95% (Confidence Interval) [CI]:1.03-22.5). Women with CIN2+ had a significantly higher viral log mean of HPV 16, (11.2 copies/ 10,000 cells; 95% CI: 9.0-13.4) than with CIN 1. The high prevalence of HPV 53 in CIN 3 and as a stand-alone genotype in the patient with invasive cervical cancer warrants that its clinical significance be further revisited among HIV-infected women. HPV 31, along with elevated means of HPV 16 viral load were predictors of CIN 2 + .

Detection of ovomucoid-specific low-affinity IgE in infants and its relationship to eczema.

PubMed

Kawamoto, Norio; Kamemura, Norio; Kido, Hiroshi; Fukao, Toshiyuki

2017-06-01

Allergen-specific low-affinity IgE was previously detected in cord blood by a highly sensitive densely carboxylated protein (DCP) chip, but not by ImmunoCAP. Here, we investigated the presence of low-affinity IgE during the early life of infants and observed its relationship with eczema. We conducted a birth cohort study, collecting sera at birth and 6 and 14 months of age (n = 110). We monitored the ovomucoid (OM)- and egg white (EW)-specific IgE (sIgE) by ImmunoCAP or DCP chip and analyzed the antigen affinity of sIgE by binding inhibition assays in the presence or absence of a mild chaotropic agent, diethyl amine (DEA). The low- and high-affinity OM-sIgEs and sensitization risk factors were analyzed by a multivariate logistic analysis. The OM-sIgE measured by DCP chip significantly correlated with that measured by ImmunoCAP, but some samples assessed as OM-sIgE positive by DCP chip were considered OM-sIgE negative by ImmunoCAP. Binding inhibition analysis after DEA treatment was performed for participants judged as OM-sIgE positive by DCP chip at 14 M. The group assessed as negative for OM- and EW-sIgE by ImmunoCAP at 6 and 14 months showed a larger binding inhibition curve shift after DEA treatment than did the group assessed as positive at these times, indicating the presence of low-affinity sIgE antibodies at 14 months. The logistic regression analysis found that persistent eczema from 6 to 14 months is a significant risk factor for developing high-affinity, but not low-affinity, sIgE. Human infant peripheral blood contains allergen-specific low-affinity sIgE. Persistent eczema is related to the development of high-affinity, but not low-affinity, IgE. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Levels of Polychlorinated Biphenyls (PCBs) and Three Organochlorine Pesticides in Fish from the Aleutian Islands of Alaska

PubMed Central

Hardell, Sara; Tilander, Hanna; Welfinger-Smith, Gretchen; Burger, Joanna; Carpenter, David O.

2010-01-01

Background Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and chlorinated pesticides, have been shown to have many adverse human health effects. These contaminants therefore may pose a risk to Alaska Natives that follow a traditional diet high in marine mammals and fish, in which POPs bioaccumulate. Methods and Findings This study examined the levels of PCBs and three pesticides [p, p′-DDE, mirex, and hexachlorobenzene (HCB)] in muscle tissue from nine fish species from several locations around the Aleutian Islands of Alaska. The highest median PCB level was found in rock sole (Lepidopsetta bilineata, 285 ppb, wet weight), while the lowest level was found in rock greenling (Hexagrammos lagocephalus, 104 ppb, wet weight). Lipid adjusted PCB values were also calculated and significant interspecies differences were found. Again, rock sole had the highest level (68,536 ppb, lipid weight). Concerning the PCB congener patterns, the more highly chlorinated congeners were most common as would be expected due to their greater persistence. Among the pesticides, p, p′-DDE generally dominated, and the highest level was found in sockeye salmon (Oncorhynchus nerka, 6.9 ppb, wet weight). The methodology developed by U.S. Environmental Protection Agency (USEPA) was used to calculate risk-based consumption limits for the analyzed fish species. For cancer health endpoints for PCBs, all species would trigger strict advisories of between two and six meals per year, depending upon species. For noncancer effects by PCBs, advisories of between seven and twenty-two meals per year were triggered. None of the pesticides triggered consumption limits. Conclusion The fish analyzed, mainly from Adak, contain significant concentrations of POPs, in particular PCBs, which raises the question whether these fish are safe to eat, particularly for sensitive populations. However when assessing any risk of the traditional diet, one must also consider the many health and cultural benefits from eating fish. PMID:20811633

Effects of dopamine D2 receptor (DRD2) and transporter (SLC6A3) polymorphisms on smoking cue-induced cigarette craving among African-American smokers.

PubMed

Erblich, J; Lerman, C; Self, D W; Diaz, G A; Bovbjerg, D H

2005-04-01

Cue-induced craving for addictive substances has long been known to contribute to the problem of persistent addiction in humans. Research in animals over the past decade has solidly established the central role of dopamine in cue-induced craving for addictive substances, including nicotine. Analogous studies in humans, however, are lacking, especially among African-American smokers, who have lower quit rates than Caucasian smokers. Based on the animal literature, the study's objective was to test the hypothesis that smokers carrying specific variants in dopamine-related genes previously associated with risk for addictive behaviors would exhibit heightened levels of cigarette craving following laboratory exposure to cues. To this end, cigarette craving was induced in healthy African-American smokers (n=88) through laboratory exposure to smoking cues. Smokers carrying either the DRD2 (D2 dopamine receptor gene) TaqI A1 RFLP or the SLC6A3 (dopamine transporter gene) 9-repeat VNTR polymorphisms had stronger cue-induced cravings than noncarriers (Ps <0.05 and 0.01, respectively). Consistent with the separate biological pathways involved (receptor, transporter), carriers of both polymorphisms had markedly higher craving responses compared to those with neither (P<0.0006), reflecting additive effects. Findings provide support for the role of dopamine in cue-induced craving in humans, and suggest a possible genetic risk factor for persistent smoking behavior in African-American smokers.

Predicting persistent posttraumatic stress disorder (PTSD) in UK military personnel who served in Iraq: a longitudinal study.

PubMed

Rona, Roberto J; Jones, Margaret; Sundin, Josefin; Goodwin, Laura; Hull, Lisa; Wessely, Simon; Fear, Nicola T

2012-09-01

In a longitudinal study we assessed which baseline risk factors are associated with persistent and partially remitted PTSD in comparison to fully remitted PTSD. 6427 (68%) of a randomly selected sample of UK service personnel completed the PTSD checklist (PCL) between 2004 and 2006 (Phase 1) and between 2007 and 2009 (Phase 2). 230 (3.9%) had possible PTSD at baseline. 66% of those with possible PTSD at baseline remitted (PCL score <30) or partially remitted (PCL score 30-49) by phase 2 of the study. Associations of persistent PTSD with the fully remitted group for risk factors at phase 1 adjusted for confounders were having discharged from service (OR 2.97, 95% CI 1.26-6.99), higher educational qualification (OR 2.74, 95% 1.23-6.08), feeling unsupported on return from deployment (OR 10.97, 95% CI 3.13-38.45), deployed not with parent unit (OR 5.63, 95% CI 1.45-21.85), multiple physical symptoms (OR 3.36, 95% CI 1.44-7.82), perception of poor or fair health (OR 2.84, 95% CI 1.28-6.27), older age and perception of risk to self (increasing with the number of events reported, p = 0.04). Deploying but not with a parent unit and psychological distress were associated in the partially remitted PTSD when compared to the fully remitted group. The positive and negative likelihood ratios for the factors most highly associated with persistent PTSD indicated they were of marginal value to identify those whose presumed PTSD would be persistent. Many factors contribute to the persistence of PTSD but none alone is useful for clinical prediction. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S.

Louisiana, now in a developmental stage of policy and planning, has completed a project aimed at reducing hazardous releases of air toxics in thee state. The state is also conducting a Comparative Risk Project and is using risk assessment practices to develop its waste quality standards. In developing an air toxic list, Louisiana incorporated four major criteria into the ranking: emission levels, human health effects, potential population exposure, and persistence or accumulation in the environment. For the human health effects criterion, data for each substance was gathered from numerous sources, although the Integrated Risk Information System (IRIS) database was usedmore » as a primary source for toxicological information. Following guidelines established by the Environmental Protection Agency (EPA), the Office of Water Resources, Water Pollution Control Division, has developed numerical criteria for human health protection based on risk assessment procedures in the 1989 Water Quality Standards Revision. Currently over 30 toxic substances have risk-based criteria for th protection of human health in the standards. Numerical criteria were calculated for carcinogenic substances having an EPA Classification of A, B1, B2, or C. Cancer class designations along with cancer potency slopes and reference doses were extracted from the IRIS database, with the exception of those chemicals that had not been assessed in IRIS as of December 1, 1988. The parameters necessary for calculating human health criteria for the missing chemicals were taken from 1980, 1984, and 1985 ambient water quality criteria documents: data on bioconcentration factors were included. Currently, Louisiana is working on a Comparative Risk Project, a ranking of the environmental issues in the state relative to potential risk to the public, which is the basis for a widespread 1991 public outreach effort.« less

The Coverage of Human Evolution in High School Biology Textbooks in the 20th Century and in Current State Science Standards

ERIC Educational Resources Information Center

Skoog, Gerald

2005-01-01

Efforts to eliminate or neutralize the coverage of evolution in high school biology textbooks in the United States have persisted with varying degrees of intensity and success since the 1920s. In particular, the coverage of human evolution has been impacted by these efforts. Evidence of the success of these efforts can be chronicled by the…

Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas' disease reactivation after heart transplantation.

PubMed

Benvenuti, Luiz A; Roggério, Alessandra; Nishiya, Anna S; Campos, Silvia V; Fiorelli, Alfredo I; Levi, José E

2014-07-01

Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 × 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49×10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior

PubMed Central

Vetreno, Ryan P.; Broadwater, Margaret A.; Robinson, Donita L.

2016-01-01

Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence. PMID:27677720

Development of risk reduction behavioral counseling for Ebola virus disease survivors enrolled in the Sierra Leone Ebola Virus Persistence Study, 2015-2016

PubMed Central

Malik, Tasneem; Ariyarajah, Archchun; Ongpin, Patricia; Hogben, Matthew; McDonald, Suzanna L. R.; Marrinan, Jaclyn; Massaquoi, Thomas; Thorson, Anna; Ervin, Elizabeth; Bernstein, Kyle; Ross, Christine; Liu, William J.; Kroeger, Karen; Durski, Kara N.; Broutet, Nathalie; Knust, Barbara; Deen, Gibrilla F.

2017-01-01

Background During the 2014–2016 West Africa Ebola Virus Disease (EVD) epidemic, the public health community had concerns that sexual transmission of the Ebola virus (EBOV) from EVD survivors was a risk, due to EBOV persistence in body fluids of EVD survivors, particularly semen. The Sierra Leone Ebola Virus Persistence Study was initiated to investigate this risk by assessing EBOV persistence in numerous body fluids of EVD survivors and providing risk reduction counseling based on test results for semen, vaginal fluid, menstrual blood, urine, rectal fluid, sweat, tears, saliva, and breast milk. This publication describes implementation of the counseling protocol and the key lessons learned. Methodology/Principal findings The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol was developed from a framework used to prevent transmission of HIV and other sexually transmitted infections. The framework helped to identify barriers to risk reduction and facilitated the development of a personalized risk-reduction plan, particularly around condom use and abstinence. Pre-test and post-test counseling sessions included risk reduction guidance, and post-test counseling was based on the participants’ individual test results. The behavioral counseling protocol enabled study staff to translate the study’s body fluid test results into individualized information for study participants. Conclusions/Significance The Ebola Virus Persistence Risk Reduction Behavioral Counseling Protocol provided guidance to mitigate the risk of EBOV transmission from EVD survivors. It has since been shared with and adapted by other EVD survivor body fluid testing programs and studies in Ebola-affected countries. PMID:28892490

Alteration of host-pathogen interactions in the wake of climate change - Increasing risk for shellfish associated infections?

PubMed

Hernroth, Bodil E; Baden, Susanne P

2018-02-01

The potential for climate-related spread of infectious diseases through marine systems has been highlighted in several reports. With this review we want to draw attention to less recognized mechanisms behind vector-borne transmission pathways to humans. We have focused on how the immune systems of edible marine shellfish, the blue mussels and Norway lobsters, are affected by climate related environmental stressors. Future ocean acidification (OA) and warming due to climate change constitute a gradually increasing persistent stress with negative trade-off for many organisms. In addition, the stress of recurrent hypoxia, inducing high levels of bioavailable manganese (Mn) is likely to increase in line with climate change. We summarized that OA, hypoxia and elevated levels of Mn did have an overall negative effect on immunity, in some cases also with synergistic effects. On the other hand, moderate increase in temperature seems to have a stimulating effect on antimicrobial activity and may in a future warming scenario counteract the negative effects. However, rising sea surface temperature and climate events causing high land run-off promote the abundance of naturally occurring pathogenic Vibrio and will in addition, bring enteric pathogens which are circulating in society into coastal waters. Moreover, the observed impairments of the immune defense enhance the persistence and occurrence of pathogens in shellfish. This may increase the risk for direct transmission of pathogens to consumers. It is thus essential that in the wake of climate change, sanitary control of coastal waters and seafood must recognize and adapt to the expected alteration of host-pathogen interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Small Ruminant Lentiviruses (SRLVs) Break the Species Barrier to Acquire New Host Range

PubMed Central

Minardi da Cruz, Juliano Cezar; Singh, Dinesh Kumar; Lamara, Ali; Chebloune, Yahia

2013-01-01

Zoonotic events of simian immunodeficiency virus (SIV) from non-human primates to humans have generated the acquired immunodeficiency syndrome (AIDS), one of the most devastating infectious disease of the last century with more than 30 million people dead and about 40.3 million people currently infected worldwide. Human immunodeficiency virus (HIV-1 and HIV-2), the two major viruses that cause AIDS in humans are retroviruses of the lentivirus genus. The genus includes arthritis-encephalitis virus (CAEV) and Maedi-Visna virus (MVV), and a heterogeneous group of viruses known as small ruminant lentiviruses (SRLVs), affecting goat and sheep. Lentivirus genome integrates into the host DNA, causing persistent infection associated with a remarkable diversity during viral replication. Direct evidence of mixed infections with these two closely related SRLVs was found in both sheep and goats. The evidence of a genetic continuum with caprine and ovine field isolates demonstrates the absence of an efficient species barrier preventing cross-species transmission. In dual-infected animals, persistent infections with both CAEV and MVV have been described, and viral chimeras have been detected. This not only complicates animal trade between countries but favors the risk that highly pathogenic variants may emerge as has already been observed in the past in Iceland and, more recently, in outbreaks with virulent strains in Spain. SRLVs affecting wildlife have already been identified, demonstrating the existence of emergent viruses adapted to new hosts. Viruses adapted to wildlife ruminants may acquire novel biopathological properties which may endanger not only the new host species but also domestic ruminants and humans. SRLVs infecting sheep and goats follow a genomic evolution similar to that observed in HIV or in other lentiviruses. Lentivirus genetic diversity and host factors leading to the establishment of naturally occurring virulent versus avirulent infections, in addition to the emergence of new strains, challenge every aspect of SRLV control measures for providing efficient tools to prevent the transmission of diseases between wild ungulates and livestock. PMID:23881276

Spatially varying density dependence drives a shifting mosaic of survival in a recovering apex predator (Canis lupus).

PubMed

O'Neil, Shawn T; Bump, Joseph K; Beyer, Dean E

2017-11-01

Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves ( Canis lupus ), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves ( C. lupus ) during a 21-year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time-dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time-dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual-level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long-term change was density-dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long-term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source-sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density-dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.

Characterizing the human postural control system using detrended fluctuation analysis

NASA Astrophysics Data System (ADS)

Teresa Blázquez, M.; Anguiano, Marta; de Saavedra, Fernando Arias; Lallena, Antonio M.; Carpena, Pedro

2010-01-01

Detrended fluctuation analysis is used to study the behaviour of the time series of the position of the center of pressure, output from the activity of a human postural control system. The results suggest that these trajectories present a crossover in their scaling properties from persistent (for high frequencies, short-range time scale) to anti-persistent (for low frequencies, long-range time scale) behaviours. The values of the scaling exponent found for the persistent parts of the trajectories are very similar for all the cases analysed. The similarity of the results obtained for the measurements done with both eyes open and both eyes closed indicate either that the visual system may be disregarded by the postural control system, while maintaining quiet standing, or that the control mechanisms associated with each type of information (visual, vestibular and somatosensory) cannot be disentangled with this technique.

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

PubMed

Serizawa, I; Amano, K; Ishii, H; Ichikawa, T; Kusaka, M; Taguchi, T; Kiyokawa, N; Fujimoto, J

2000-06-01

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage. Copyright 2000 Academic Press.

The Spatial Scaling of Global Rainfall Extremes

NASA Astrophysics Data System (ADS)

Devineni, N.; Xi, C.; Lall, U.; Rahill-Marier, B.

2013-12-01

Floods associated with severe storms are a significant source of risk for property, life and supply chains. These property losses tend to be determined as much by the duration of flooding as by the depth and velocity of inundation. High duration floods are typically induced by persistent rainfall (upto 30 day duration) as seen recently in Thailand, Pakistan, the Ohio and the Mississippi Rivers, France, and Germany. Events related to persistent and recurrent rainfall appear to correspond to the persistence of specific global climate patterns that may be identifiable from global, historical data fields, and also from climate models that project future conditions. A clear understanding of the space-time rainfall patterns for events or for a season will enable in assessing the spatial distribution of areas likely to have a high/low inundation potential for each type of rainfall forcing. In this paper, we investigate the statistical properties of the spatial manifestation of the rainfall exceedances. We also investigate the connection of persistent rainfall events at different latitudinal bands to large-scale climate phenomena such as ENSO. Finally, we present the scaling phenomena of contiguous flooded areas as a result of large scale organization of long duration rainfall events. This can be used for spatially distributed flood risk assessment conditional on a particular rainfall scenario. Statistical models for spatio-temporal loss simulation including model uncertainty to support regional and portfolio analysis can be developed.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain

PubMed Central

Li, Zhe; Tseng, Pang-Yen; Tiwari, Vinod; Xu, Qian; He, Shao-Qiu; Wang, Yan; Zheng, Qin; Han, Liang; Wu, Zhiping; Blobaum, Anna L.; Cui, Yiyuan; Tiwari, Vineeta; Sun, Shuohao; Cheng, Yingying; Huang-Lionnet, Julie H. Y.; Geng, Yixun; Xiao, Bo; Peng, Junmin; Hopkins, Corey; Raja, Srinivasa N.; Guan, Yun; Dong, Xinzhong

2017-01-01

Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across Mrgprs, drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse Mrgprs with human MrgprX1. This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8–22 (BAM8–22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1. Cellular studies suggested that ML382 enhances the ability of BAM8–22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission. Importantly, both BAM8–22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in MrgprX1 mice after nerve injury without acquiring coadministration of an exogenous agonist. Our findings suggest that humanized MrgprX1 mice provide a promising preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain. PMID:28223516

The natural course of anxiety symptoms in early adolescence: factors related to persistence.

PubMed

Voltas, Núria; Hernández-Martínez, Carmen; Arija, Victoria; Canals, Josefa

2017-11-01

Anxiety disorders are the most common mental health problems during childhood and adolescence. This study examined the course of anxiety symptoms in early adolescents from the general population over three phases. Prospective cohort study. Two hundred and forty-two participants (mean-age of 13.52) from a baseline sample of 1514 (mean-age of 10.23) were followed up three times. Of the 1514 children, those with emotional risk and controls without risk constituted the second-phase sample (n = 562; mean-age of 11.25). The Screen for Child Anxiety Related Emotional Disorders-SCARED was administered in all three phases. Fifty-six percent and 32% of respondents showed total scores above the SCARED cutoff point at one and three years follow-up, respectively. Eight percent showed fluctuating symptoms. Fifty-five percent of respondents showed high scores for any subtype of anxiety over three years. Social phobia and generalized anxiety symptoms were the most prevalent and persistent. Participants with persistent separation anxiety showed the highest co-occurrence with symptoms of other psychopathological disorders. Participants with persistent anxiety showed lower academic performance. Being male was a protective factor against persistence. The data support anxiety maintenance during early adolescence. Early adolescence is a critical period which may involve other serious academic, social, and family problems.

Oral anticoagulant persistence in patients with non-valvular atrial fibrillation: A cohort study using primary care data in Germany

PubMed Central

Lefèvre, Cinira; Evans, David; Hack, Guido; Stynes, Gillian; Maguire, Andrew

2017-01-01

This study examined characteristics and treatment persistence among patients prescribed oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). We identified 15,244 patients (51.8% male, 72.7% aged ≥70) with NVAF and no prior OAC therapy who were prescribed apixaban (n = 1,303), rivaroxaban (n = 5,742), dabigatran (n = 1,622) or vitamin-K antagonists (VKAs, n = 6,577) between 1-Dec-2012 and 31-Oct-2014 in German primary care (IMS® Disease Analyzer). We compared OAC persistence using Cox regression over patients’ entire follow-up and using a data-driven time-partitioned approach (before/after 100 days) to handle non-proportional hazards. History of stroke risk factors (stroke/transient ischaemic attack [TIA] 15.2%; thromboembolism 14.1%; hypertension 84.3%) and high bleeding risk (HAS-BLED score≥3 68.4%) was common. Apixaban-prescribed patients had more frequent history of stroke/TIA (19.7%) and high bleeding risk (72.6%) than other OACs. 12-month persistence rates were: VKA 57.5% (95% confidence interval (CI) 56.0–59.0%), rivaroxaban 56.6% (54.9–58.2%), dabigatran 50.1% (47.2–53.1%), apixaban 62.9% (58.8–67.0%). Over entire follow-up, compared to VKA, non-persistence was similar with apixaban (adjusted hazard ratio 1.08, 95% CI 0.95–1.24) but higher with rivaroxaban (1.21, 1.14–1.29) and dabigatran (1.53, 1.40–1.68). Using post-hoc time-partitioned approach: in first 100 days, non-persistence was higher with apixaban (1.37, 1.17–1.59), rivaroxaban (1.41, 1.30–1.53) and dabigatran (1.91, 1.70–2.14) compared to VKA. Compared to apixaban, rivaroxaban non-persistence was similar (1.03, 0.89–1.20), dabigatran was higher (1.39, 1.17–1.66). After 100 days, apixaban non-persistence was lower than VKA (0.66, 0.52–0.85); rivaroxaban (0.97, 0.87–1.07) and dabigatran (1.10, 0.95–1.28) were similar to VKA. Furthermore, rivaroxaban (1.46, 1.13–1.88) and dabigatran (1.67, 1.26–2.19) non-persistence was higher than apixaban. This study describes real-world observations on OAC use, particularly early apixaban use following approval for NVAF, in Germany. We identified potential differential OAC prescribing and higher persistence with apixaban than other OACs after 100 days’ treatment. Larger studies are needed with longer follow-up to establish long-term patterns. PMID:29016695

Anorexia Nervosa and its Associated Endocrinopathy in Young People

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2016-01-01

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to low BMI, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high PYY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN, however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

PubMed

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Pathogenicity of Exopolysaccharide-Producing Actinomyces oris Isolated from an Apical Abscess Lesion

DTIC Science & Technology

2013-01-01

sugars with man- nose constituting 77.5% of the polysaccharides . Strain K20 induced persistent abscesses in mice lasting at least 5 days at a... polysaccharides (EPSs) could contribute to their survival and the development of persistent infections in the human body (Costerton et al. 1999). For example...High-performance liquid chromatography (HPLC) analysis of EPSs Neutral monosaccharides were released from purified EPS (5 mg) by hydrolysis in a

Factors associated with persistent hypertension after puerperium among women with pre-eclampsia/eclampsia in Mulago hospital, Uganda.

PubMed

Ndayambagye, Emmanuel B; Nakalembe, Miriam; Kaye, Dan K

2010-03-12

Women with severe pre-eclampsia/eclampsia are at risk of developing chronic hypertension in future. Chronic hypertension may manifest initially as persistent hypertension at the end of the puerperium. The objective was to determine the incidence and maternal biochemical, hematological and socio-demographic risk factors for persistent hypertension in patients with pre-eclampsia/eclampsia. This was a prospective cohort study conducted from November 2008 to May 2009 at Mulago hospital labor ward and postnatal clinic. Participants were 200 women managed for pre-eclampsia/eclampsia and followed up to the end of the puerperium. Data was collected through using pre-coded interviewer-administered questionnaires, checking medical records and laboratory investigations. STATA (release 9) software was used for data analysis. At bivariate analysis, the relative risk of persistent hypertension was estimated at the 95% confidence level. Using multivariate logistic regression analysis, factors that were independently associated with persistent hypertension were evaluated. Fifty four (27.7%) out of the total 195 women had persistent hypertension after puerperium. Serum creatinine and the age of the patient were the only factors associated with persistence of hypertension after puerperium. Nearly every one in four mothers with pre-eclampsia/eclampsia are at risk of persistent hypertension after the puerperium. Serum creatinine, serum uric acid and participants' age were the only factors independently associated with persistence of hypertension after the puerperium.

Analysis of longitudinal multivariate outcome data from couples cohort studies: application to HPV transmission dynamics

PubMed Central

Kong, Xiangrong; Wang, Mei-Cheng; Gray, Ronald

2014-01-01

We consider a specific situation of correlated data where multiple outcomes are repeatedly measured on each member of a couple. Such multivariate longitudinal data from couples may exhibit multi-faceted correlations which can be further complicated if there are polygamous partnerships. An example is data from cohort studies on human papillomavirus (HPV) transmission dynamics in heterosexual couples. HPV is a common sexually transmitted disease with 14 known oncogenic types causing anogenital cancers. The binary outcomes on the multiple types measured in couples over time may introduce inter-type, intra-couple, and temporal correlations. Simple analysis using generalized estimating equations or random effects models lacks interpretability and cannot fully utilize the available information. We developed a hybrid modeling strategy using Markov transition models together with pairwise composite likelihood for analyzing such data. The method can be used to identify risk factors associated with HPV transmission and persistence, estimate difference in risks between male-to-female and female-to-male HPV transmission, compare type-specific transmission risks within couples, and characterize the inter-type and intra-couple associations. Applying the method to HPV couple data collected in a Ugandan male circumcision (MC) trial, we assessed the effect of MC and the role of gender on risks of HPV transmission and persistence. PMID:26195849

Occurrence of selected pharmaceuticals in the principal sewage treatment plants in Rome (Italy) and in the receiving surface waters.

PubMed

Patrolecco, Luisa; Capri, Silvio; Ademollo, Nicoletta

2015-04-01

This paper provides data on the occurrence of selected human pharmaceuticals (carbamazepine, clofibric acid, diclofenac, fenofibrate, fenoprofen, gemfibrozil, ibuprofen, ketoprofen, and naproxen) including steroid hormones (17β-estradiol, 17α-ethinylestradiol, and estrone) in influents/effluents to/from the four principal wastewater treatment plants (WWTPs) serving the city of Rome (Italy), in two different sampling campaigns. Target compounds were also analyzed in the receiving River Tiber and River Aniene. Analytical determination was carried out by LC-MS/MS after sample cleanup and concentration by off-line solid-phase extraction (SPE). The aim of the study was to increase the information currently available on the presence and persistence of pharmaceuticals in Italian urban wastewaters and to evaluate the environmental impact of the pharmaceutical residues discharged through effluents into the receiving rivers. Results indicated that after the treatment processes, most of pharmaceuticals were not completely eliminated, as average removal efficiencies were in the 14-100% wide range during both sampling periods, with higher yields in spring than in winter. Levels detected in overall samples ranged from 5 to 2,230 ng/L in influents and from 5 to 1,424 ng/L in effluents. Carbamazepine, diclofenac, ibuprofen, and gemfibrozil showed the highest persistence to removal. Concentrations in the receiving waters were about one order of magnitude lower than in effluents, with a tendency to increase progressively through the urban tract of the river. Finally, an environmental risk analysis showed that carbamazepine, gemfibrozil, and estrone can pose a high risk at the concentrations detected in effluents and a medium risk in rivers, highlighting their potential hazard for the health of the aquatic ecosystem.

Consumption of organic meat does not diminish the carcinogenic potential associated with the intake of persistent organic pollutants (POPs).

PubMed

Hernández, Ángel Rodríguez; Boada, Luis D; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valerón, Pilar F; Camacho, María; Zumbado, Manuel; Almeida-González, Maira; Henríquez-Hernández, Luis A; Luzardo, Octavio P

2017-02-01

Numerous studies have shown an epidemiological link between meat consumption and the incidence of cancer, and it has been suggested that this relationship may be motivated by the presence of carcinogenic contaminants on it. Among the most frequently detected contaminants in meat are several types of persistent organic pollutants (POPs), and it is well known that many of them are carcinogenic. On the other hand, an increasing number of consumers choose to feed on what are perceived as healthier foods. Thus, the number of consumers of organic food is growing. However, environmental contamination by POPs is ubiquitous, and it is therefore unlikely that the practices of organic food production are able to prevent this contamination. To test this hypothesis, we acquired 76 samples of meat (beef, chicken, and lamb) of two modes of production (organic and conventional) and quantified their levels of 33 carcinogenic POPs. On this basis, we determined the human meat-related daily dietary exposure to these carcinogens using as a model a population with a high consumption of meat, such as the Spanish population. The maximum allowable meat consumption for this population and the carcinogenic risk quotients associated with the current pattern of consumption were calculated. As expected, no sample was completely free of carcinogenic contaminants, and the differences between organically and conventionally produced meats were minimal. According to these results, the current pattern of meat consumption exceeded the maximum limits, which are set according to the levels of contaminations, and this is associated with a relevant carcinogenic risk. Strikingly, the consumption of organically produced meat does not diminish this carcinogenic risk, but on the contrary, it seems to be even higher, especially that associated with lamb consumption.

Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence

PubMed Central

Poquet, Yannick; Levillain, Florence; Botanch, Catherine; Bardou, Fabienne; Daffé, Mamadou; Emile, Jean-François; Marchou, Bruno; Cardona, Pere-Joan; de Chastellier, Chantal; Altare, Frédéric

2008-01-01

Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis–infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria. PMID:19002241

Assessing Lead, Nickel, and Zinc Pollution in Topsoil from a Historic Shooting Range Rehabilitated into a Public Urban Park

PubMed Central

Argyraki, Ariadne; Ornelas-Soto, Nancy

2017-01-01

Soil contamination is a persistent problem in the world. The redevelopment of a site with a historical deposition of metals might conceal the threat of remaining pollution, especially when the site has become a public place. In this study, human health risk assessment is performed after defining the concentrations of Pb, Ni, and Zn in the topsoil of a former shooting range rehabilitated into a public park in the Municipality of Kesariani (Athens, Greece). A methodology that uses inductively coupled plasma mass spectrometry (ICP-MS, 13 samples), another that uses portable X-ray fluorescence (XRF) following a dense sample design (91 samples), and a hybrid approach that combines both, were used to obtain the concentrations of the trace elements. The enrichment factor and geoacummulation index were calculated to define the degree of pollution of the site. The hazard quotient and cancer risk indicators were also computed to find the risk to which the population is exposed. The present study reveals high non-carcinogenic health risk due to Pb pollution with ingestion as the main exposure pathway. The carcinogenic risk for Pb is within tolerable limits, but the definition of land use might alter such a statement. Lastly, regarding Ni and Zn, the site is unpolluted and there is insignificant carcinogenic and non-carcinogenic risks. PMID:28665307

Assessing Lead, Nickel, and Zinc Pollution in Topsoil from a Historic Shooting Range Rehabilitated into a Public Urban Park.

PubMed

Urrutia-Goyes, Ricardo; Argyraki, Ariadne; Ornelas-Soto, Nancy

2017-06-30

Soil contamination is a persistent problem in the world. The redevelopment of a site with a historical deposition of metals might conceal the threat of remaining pollution, especially when the site has become a public place. In this study, human health risk assessment is performed after defining the concentrations of Pb, Ni, and Zn in the topsoil of a former shooting range rehabilitated into a public park in the Municipality of Kesariani (Athens, Greece). A methodology that uses inductively coupled plasma mass spectrometry (ICP-MS, 13 samples), another that uses portable X-ray fluorescence (XRF) following a dense sample design (91 samples), and a hybrid approach that combines both, were used to obtain the concentrations of the trace elements. The enrichment factor and geoacummulation index were calculated to define the degree of pollution of the site. The hazard quotient and cancer risk indicators were also computed to find the risk to which the population is exposed. The present study reveals high non-carcinogenic health risk due to Pb pollution with ingestion as the main exposure pathway. The carcinogenic risk for Pb is within tolerable limits, but the definition of land use might alter such a statement. Lastly, regarding Ni and Zn, the site is unpolluted and there is insignificant carcinogenic and non-carcinogenic risks.

Epigenetic Changes in Diabetes and Cardiovascular Risk

PubMed Central

Keating, Samuel T; Plutzky, Jorge; El-Osta, Assam

2016-01-01

Cardiovascular complications remain the leading causes of morbidity and premature mortality in patients with diabetes. Studies in humans and preclinical models demonstrate lasting gene expression changes in the vasculopathies initiated by previous exposure to high glucose concentrations and the associated overproduction of reactive oxygen species. The molecular signatures of chromatin architectures that sensitize the genome to these and other cardiometabolic risk factors of the diabetic milieu are increasingly implicated in the biologic memory underlying cardiovascular complications and now widely considered as promising therapeutic targets. Atherosclerosis is a complex heterocellular disease where the contributing cell types possess distinct epigenomes shaping diverse gene expression. While the extent that pathological chromatin changes can be manipulated in human cardiovascular disease remains to be established, the clinical applicability of epigenetic interventions will be greatly advanced by a deeper understanding of the cell type-specific roles played by writers, erasers, and readers of chromatin modifications in the diabetic vasculature. This review details a current perspective of epigenetic mechanisms of macrovascular disease in diabetes, and highlights recent key descriptions of chromatinized changes associated with persistent gene expression in endothelial, smooth muscle, and circulating immune cells relevant to atherosclerosis. Furthermore we discuss the challenges associated with pharmacological targeting of epigenetic networks to correct abnormal or deregulated gene expression as a strategy to alleviate the clinical burden of diabetic cardiovascular disease. PMID:27230637

The assessment of seafarers' knowledge, attitudes and practices related to STI/HIV/AIDS in northern Morocco.

PubMed

Laraqui, Salwa; Laraqui, Omar; Manar, Nadia; Ghailan, Tarik; Belabsir, Mohamed; Deschamps, Frederic; Laraqui, Chakib H

2017-01-01

The purpose of this study was to assess the knowledge, attitudes and practices of seafarers in relation to sexually transmitted infections (STI) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). This transversal, descriptive and behavioural study was conducted in 2014 on a representative sample of 1447 seafarers. The rate of participation was 95%. The mean age was 36.1 ± 8.2 years. Knowledge about transmission and prevention mode was satisfactory on HIV/AIDS; however, some misconceptions still persist. The level of stigmatisation and discrimination towards people living with the virus was considered high. The prevalence of sexual high-risk behaviour was significant: 32% had at least two sexual partners and 26.3% have had sex with sex workers, 60% of them were not protected; 42.8% have never used the condom and only 15.1% used it systematically. The sailors who had sexual intercourse under the influence of alcohol or drugs are less protected. As too HIV testing, only 10.2% did it. This study showed a gap in knowledge about transmission and prevention of HIV infection/AIDS and sexual risk behaviour. Increasing awareness and information among seafarers is of prime importance.

Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case-control analysis.

PubMed

Cotté, François-Emery; Mercier, Florence; De Pouvourville, Gérard

2008-12-01

Nonadherence to treatment is an important determinant of long-term outcomes in women with osteoporosis. This study was conducted to investigate the association between adherence and osteoporotic fracture risk and to identify optimal thresholds for good compliance and persistence. A secondary objective was to perform a preliminary evaluation of the cost consequences of adherence. This was a retrospective case-control analysis. Data were derived from the Thales prescription database, which contains information on >1.6 million patients in the primary health care setting in France. Cases were women aged >or=50 years who had an osteoporosis-related fracture in 2006. For each case, 5 matched controls were randomly selected. Both compliance and persistence aspects of treatment adherence were examined. Compliance was estimated based on the medication possession ratio (MPR). Persistence was calculated as the time from the initial filling of a prescription for osteoporosis medication until its discontinuation. The mean (SD) MPR was lower in cases compared with controls (58.8% [34.7%] vs 72.1% [28.8%], respectively; P < 0.001). Cases were more likely than controls to discontinue osteoporosis treatment (50.0% vs 25.3%; P < 0.001), yielding a significantly lower proportion of patients who were still persistent at 1 year (34.1% vs 40.9%; P < 0.001). MPR was the best predictor of fracture risk, with an area under the receiver-operating-characteristic curve that was higher than that for persistence (0.59 vs 0.55). The optimal MPR threshold for predicting fracture risk was >or=68.0%. Compared with less-compliant women, women who achieved this threshold had a 51% reduction in fracture risk. The difference in annual drug expenditure between women achieving this threshold and those who did not was approximately euro300. The optimal threshold for persistence with therapy was at least 6 months. Attaining this threshold was associated with a 28% reduction in fracture risk compared with less-persistent women. In this study, better treatment adherence was associated with a greater reduction in fracture risk. Compliance appeared to predict fracture risk better than did persistence.

In Situ Detection of Regulatory T Cells in Human Genital Herpes Simplex Virus Type 2 (HSV-2) Reactivation and Their Influence on Spontaneous HSV-2 Reactivation

PubMed Central

Milman, Neta; Zhu, Jia; Johnston, Christine; Cheng, Anqi; Magaret, Amalia; Koelle, David M.; Huang, Meei-Li; Jin, Lei; Klock, Alexis; Layton, Erik D.; Corey, Lawrence

2016-01-01

Background. Herpes simplex virus type 2 (HSV-2) reactivation is accompanied by a sustained influx of CD4+ and CD8+ T cells that persist in genital tissue for extended periods. While CD4+ T cells have long been recognized as being present in herpetic ulcerations, their role in subclinical reactivation and persistence is less well known, especially the role of CD4+ regulatory T cells (Tregs). Methods. We characterized the Treg (CD4+Foxp3+) population during human HSV-2 reactivation in situ in sequential genital skin biopsy specimens obtained from HSV-2–seropositive subjects at the time of lesion onset up to 8 weeks after healing. Results. High numbers of Tregs infiltrated to the site of viral reactivation and persisted in proximity to conventional CD4+ T cells (Tconvs) and CD8+ T cells. Treg density peaked during the lesion stage of the reactivation. The number of Tregs from all time points (lesion, healed, 2 weeks after healing, 4 weeks after healing, and 8 weeks after healing) was significantly higher than in control biopsy specimens from unaffected skin. There was a direct correlation between HSV-2 titer and Treg density. Conclusions. The association of a high Treg to Tconv ratio with high viral shedding suggests that the balance between regulatory and effector T cells influences human HSV-2 disease. PMID:27117511

Revolatilization of persistent organic pollutants in the Arctic induced by climate change

NASA Astrophysics Data System (ADS)

Ma, Jianmin; Hung, Hayley; Tian, Chongguo; Kallenborn, Roland

2011-08-01

Persistent organic pollutants (POPs) are organic compounds produced by human activities that are resistant to environmental degradation. They include industrial chemicals, such as polychlorinated biphenyls, and pesticides, such as dichlorodiphenyltrichloroethane. Owing to their persistence in the environment, POPs are transported long distances in the atmosphere, accumulating in regions such as the Arctic, where low temperatures induce their deposition. Here the compounds accumulate in wildlife and humans, putting their health at risk. The concentrations of many POPs have decreased in Arctic air over the past few decades owing to restrictions on their production and use. As the climate warms, however, POPs deposited in sinks such as water and ice are expected to revolatilize into the atmosphere, and there is evidence that this process may have already begun for volatile compounds. Here we show that many POPs, including those with lower volatilities, are being remobilized into the air from repositories in the Arctic region as a result of sea-ice retreat and rising temperatures. We analysed records of the concentrations of POPs in Arctic air since the early 1990s and compared the results with model simulations of the effect of climate change on their atmospheric abundances. Our results indicate that a wide range of POPs have been remobilized into the Arctic atmosphere over the past two decades as a result of climate change, confirming that Arctic warming could undermine global efforts to reduce environmental and human exposure to these toxic chemicals.

Screening for Dyslexia Using Eye Tracking during Reading.

PubMed

Nilsson Benfatto, Mattias; Öqvist Seimyr, Gustaf; Ygge, Jan; Pansell, Tony; Rydberg, Agneta; Jacobson, Christer

2016-01-01

Dyslexia is a neurodevelopmental reading disability estimated to affect 5-10% of the population. While there is yet no full understanding of the cause of dyslexia, or agreement on its precise definition, it is certain that many individuals suffer persistent problems in learning to read for no apparent reason. Although it is generally agreed that early intervention is the best form of support for children with dyslexia, there is still a lack of efficient and objective means to help identify those at risk during the early years of school. Here we show that it is possible to identify 9-10 year old individuals at risk of persistent reading difficulties by using eye tracking during reading to probe the processes that underlie reading ability. In contrast to current screening methods, which rely on oral or written tests, eye tracking does not depend on the subject to produce some overt verbal response and thus provides a natural means to objectively assess the reading process as it unfolds in real-time. Our study is based on a sample of 97 high-risk subjects with early identified word decoding difficulties and a control group of 88 low-risk subjects. These subjects were selected from a larger population of 2165 school children attending second grade. Using predictive modeling and statistical resampling techniques, we develop classification models from eye tracking records less than one minute in duration and show that the models are able to differentiate high-risk subjects from low-risk subjects with high accuracy. Although dyslexia is fundamentally a language-based learning disability, our results suggest that eye movements in reading can be highly predictive of individual reading ability and that eye tracking can be an efficient means to identify children at risk of long-term reading difficulties.

Risk factors for lack of statin therapy in patients with diabetes and coronary artery disease.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

Patients with both diabetes and coronary artery disease (CAD) have exceedingly high cardiovascular risk. Nevertheless, little is known about prevalence of statin therapy in this population and reasons why some patients may not be receiving this potentially life-saving treatment. To investigate prevalence and predictors of statin therapy in patients with combined diabetes and CAD. We conducted a retrospective cohort study of primary care patients with diabetes and CAD followed at 2 academic medical centers between 2000 and 2011. We used multivariable logistic regression to identify patient and provider characteristics associated with (1) statin initiation (any history of statin therapy) and (2) statin persistence (active statin prescription at the study end). Of 8488 study patients, 7427 (87.5%) ever received statins and 6212 (73.2%) had persistent statin therapy. Younger age (odds ratio [OR], 1.26 per decade), smoking (OR, 1.49) and cardiologist evaluation (OR, 2.26) were associated with statin initiation (P < .0001 for all). Younger age (OR, 1.17), family history of CAD (OR, 1.39), no adverse reactions to statins (OR, 1.40; P < .0001 for all), female sex (OR, 1.22; P = .005), history of smoking (OR, 1.22; P = .003), cardiologist evaluation (OR, 1.23; P = .002), and lower HbA1c (OR, 1.04; P = 0.003) were associated with persistent statin therapy. Only 362 (29.8%) of the 1215 patients without persistent statin therapy had tried at least 2 statins, and 58 (4.8%) tried 3 statins. Many patients with combined CAD and diabetes are not treated with statins, although in this very high-risk group, even moderate-intensity statins result in meaningful reductions in cardiovascular events. Higher cardiovascular risk and cardiologist evaluation were associated with higher prevalence of statin therapy. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The Natural History of Oral Human Papillomavirus in Young Costa Rican Women.

PubMed

Beachler, Daniel C; Lang Kuhs, Krystle A; Struijk, Linda; Schussler, John; Herrero, Rolando; Porras, Carolina; Hildesheim, Allan; Cortes, Bernal; Sampson, Joshua; Quint, Wim; Gonzalez, Paula; Kreimer, Aimée R

2017-07-01

Oral human papillomavirus (HPV) infection and related oropharyngeal cancer are uncommon in lower-income countries, particularly compared to HPV-associated cervical cancer. However, little is known about the natural history of oral HPV in less-developed settings and how it compares to the natural history of cervical HPV. Three hundred fifty women aged 22 to 33 years from the Costa Rica Vaccine Trial provided exfoliated cells from the cervical and oral regions at 2 visits 2 years apart. Samples from both visits were tested for 25 characterized α HPV types by the SPF10 PCR-DNA enzyme immunoassay-LiPA25 version 1 system. Risk factors for oral HPV persistence were calculated utilizing generalized estimating equations with a logistic link. Among the 82 women with characterized α oral HPV DNA detected at baseline, 14 persisted and were detected 2 years later (17.6%; 95% confidence interval [CI], 10.9-28.5%) and was similar to the persistence of α cervical HPV (40/223; 17.7%; 95% CI, 13.1-23.9%; P = 0.86). Acquisition of new α oral HPV type was low; incident infection (1.7%; 95% CI, 0.6-3.7%). Oral HPV DNA is uncommon in young women in Latin America, and often appears to clear within a few years at similar rates to cervical HPV.

Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia.

PubMed

Reynolds, C; Roderick, J E; LaBelle, J L; Bird, G; Mathieu, R; Bodaar, K; Colon, D; Pyati, U; Stevenson, K E; Qi, J; Harris, M; Silverman, L B; Sallan, S E; Bradner, J E; Neuberg, D S; Look, A T; Walensky, L D; Kelliher, M A; Gutierrez, A

2014-09-01

Treatment resistance in T-cell acute lymphoblastic leukemia (T-ALL) is associated with phosphatase and tensin homolog (PTEN) deletions and resultant phosphatidylinositol 3'-kinase (PI3K)-AKT pathway activation, as well as MYC overexpression, and these pathways repress mitochondrial apoptosis in established T-lymphoblasts through poorly defined mechanisms. Normal T-cell progenitors are hypersensitive to mitochondrial apoptosis, a phenotype that is dependent on the expression of proapoptotic BIM. In a conditional zebrafish model, MYC downregulation induced BIM expression in T-lymphoblasts, an effect that was blunted by expression of constitutively active AKT. In human T-ALL cell lines and treatment-resistant patient samples, treatment with MYC or PI3K-AKT pathway inhibitors each induced BIM upregulation and apoptosis, indicating that BIM is repressed downstream of MYC and PI3K-AKT in high-risk T-ALL. Restoring BIM function in human T-ALL cells using a stapled peptide mimetic of the BIM BH3 domain had therapeutic activity, indicating that BIM repression is required for T-ALL viability. In the zebrafish model, where MYC downregulation induces T-ALL regression via mitochondrial apoptosis, T-ALL persisted despite MYC downregulation in 10% of bim wild-type zebrafish, 18% of bim heterozygotes and in 33% of bim homozygous mutants (P=0.017). We conclude that downregulation of BIM represents a key survival signal downstream of oncogenic MYC and PI3K-AKT signaling in treatment-resistant T-ALL.

Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types.

PubMed

Phongsavan, Keokedthong; Gustavsson, Inger; Marions, Lena; Phengsavanh, Alongkone; Wahlström, Rolf; Gyllensten, Ulf

2012-10-01

Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

What girls won't do for love: human immunodeficiency virus/sexually transmitted infections risk among young African-American women driven by a relationship imperative.

PubMed

Raiford, Jerris L; Seth, Puja; DiClemente, Ralph J

2013-05-01

Rates of Human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) continue to increase among African-American youth. Adolescents who have a stronger identity in relation to others (relational identity) rather than to themselves (self-identity) may view intimate relationships as imperative to a positive self-concept, which may lead to risky sexual behavior and abuse. Therefore, the present study assessed the associations among a relationship imperative and HIV/STI-related risk factors and behaviors. Participants were 715 African-American adolescent females, aged 15 to 21 years. They completed measures that assessed how important a relationship was to them and HIV-related risk factors and behaviors. Participants also provided vaginal swab specimens for STI testing. Multivariate logistic regression analyses, controlling for covariates, were conducted. Females who endorsed a relationship imperative (29%), compared to those who did not, were more likely to report: unprotected sex, less power in their relationships, perceived inability to refuse sex, anal sex, sex while their partner was high on alcohol/drugs, and partner abuse. Furthermore, participants with less power, recent partner abuse, and a perceived ability to refuse sex were more likely to test STI positive. These results indicate that if African-American adolescent females believe a relationship is imperative, they are more likely to engage in riskier sexual behaviors. Additionally, less perceived power and partner abuse increases their risk for STIs. HIV/STI prevention programs should target males and females and address healthy relationships, sense of self-worth, self-esteem and the gender power imbalance that may persist in the community along with HIV/STI risk. Published by Elsevier Inc.

DDT Exposure in Utero and Breast Cancer

PubMed Central

La Merrill, Michele; Krigbaum, Nickilou Y.; Yeh, Gregory; Park, June-Soo; Zimmermann, Lauren; Cirillo, Piera M.

2015-01-01

Context: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation. Hypothesis: In utero exposure to DDT is associated with an increased risk of breast cancer. Design: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year). Setting and Participants: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study. Main Outcome Measure: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured. Results: Maternal o,p′-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5–9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings. Conclusions: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk. PMID:26079774

Importance of Nutrients and Nutrient Metabolism on Human Health

PubMed Central

Chen, Yiheng; Michalak, Marek; Agellon, Luis B.

2018-01-01

Nutrition transition, which includes a change from consumption of traditional to modern diets that feature high-energy density and low nutrient diversity, is associated with acquired metabolic syndromes. The human diet is comprised of diverse components which include both nutrients, supplying the raw materials that drive multiple metabolic processes in every cell of the body, and non-nutrients. These components and their metabolites can also regulate gene expression and cellular function via a variety of mechanisms. Some of these components are beneficial while others have toxic effects. Studies have found that persistent disturbance of nutrient metabolism and/or energy homeostasis, caused by either nutrient deficiency or excess, induces cellular stress leading to metabolic dysregulation and tissue damage, and eventually to development of acquired metabolic syndromes. It is now evident that metabolism is influenced by extrinsic factors (e.g., food, xenobiotics, environment), intrinsic factors (e.g., sex, age, gene variations) as well as host/microbiota interaction, that together modify the risk for developing various acquired metabolic diseases. It is also becoming apparent that intake of diets with low-energy density but high in nutrient diversity may be the key to promoting and maintaining optimal health.

Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates.

PubMed

Thompson, Jacqueline R; Valleau, Jeanette C; Barling, Ashley N; Franco, Juliana G; DeCapo, Madison; Bagley, Jennifer L; Sullivan, Elinor L

2017-01-01

Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations.

Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates

PubMed Central

Thompson, Jacqueline R.; Valleau, Jeanette C.; Barling, Ashley N.; Franco, Juliana G.; DeCapo, Madison; Bagley, Jennifer L.; Sullivan, Elinor L.

2017-01-01

Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations. PMID:28785241

Tidal saltmarsh fragmentation and persistence of San Pablo Song Sparrows (Melospiza melodia samuelis): Assessing benefits of wetland restoration in San Francisco Bay

USGS Publications Warehouse

Takekawa, John Y.; Sacks, B.N.; Woo, I.; Johnson, M.L.; Wylie, G.D.; ,

2006-01-01

The San Pablo Song Sparrow (Melospiza melodia samuelis) is one of three morphologically distinct Song Sparrow subspecies in tidal marshes of the San Francisco Bay estuary. These subspecies are rare, because as the human population has grown, diking and development have resulted in loss of 79% of the historic tidal marshes. Hundreds of projects have been proposed in the past decade to restore tidal marshes and benefit endemic populations. To evaluate the value of these restoration projects for Song Sparrows, we developed a population viability analysis (PVA) model to examine persistence of samuelis subspecies in relation to parcel size, connectivity, and catastrophe in San Pablo Bay. A total of 101 wetland parcels were identified from coverages of modern and historic tidal marshes. Parcels were grouped into eight fragments in the historical landscape and 10 in the present landscape. Fragments were defined as a group of parcels separated by >1 km, a distance that precluded regular interchange. Simulations indicated that the historic (circa 1850) samuelis population was three times larger than the modern population. However, only very high levels (>70% mortality) of catastrophe would threaten their persistence. Persistence of populations was sensitive to parcel size at a carrying capacity of <10 pairs, but connectivity of parcels was found to have little importance because habitats were dominated by a few large parcels. Our analysis indicates little risk of extinction of the samuelis subspecies with the current extent of tidal marshes, but the vulnerability of the small-est parcels suggests that restoration should create larger continuous tracts. Thus, PVA models may be useful tools for balancing the costs and benefits of restoring habitats for threatened tidal-marsh populations in wetland restoration planning.

A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-positive and HIV-negative Women in Senegal, Africa

PubMed Central

Whitham, Hilary K.; Hawes, Stephen E.; Chu, Haitao; Oakes, J. Michael; Lifson, Alan R.; Kiviat, Nancy B.; Sow, Papa Salif; Gottlieb, Geoffrey S.; Ba, Selly; Sy, Marie P.; Kulasingam, Shalini L.

2017-01-01

Background There is evidence of an interaction between human immunodeficiency virus (HIV) and human papillomavirus (HPV) resulting in increased HPV-associated morbidity and cancer mortality among HIV-positive women. This study aims to determine how the natural history of cervical HPV infection differs by HIV status. Methods A total of 1,320 women (47% were positive for HIV-1 and/or HIV-2) were followed for an average of two years in Senegal, West Africa between 1994 and 2010. Cytology (with a sub-sample of histology) and HPV DNA testing were performed at approximately 4-month intervals yielding data from over 7,900 clinic visits. Competing risk modeling was used to estimate rates for transitioning between three clinically relevant natural history stages: Normal, HPV, and HSIL (high-grade squamous intraepithelial lesions). Among HIV-positive women, exploratory univariate analyses were conducted examining the impact of HPV type, infection with multiple HPV types, HIV type, CD4+ count, and age. Results HIV-positive women had higher rates of progression and lower rates of regression compared to HIV-negative women (i.e. adverse transitions). HIV-positive women had a 2.55 (95% CI: 1.69–3.86; P < 0.0001) times higher rate of progression from HPV to HSIL than HIV-negative women (with 24-month absolute risks of 0.18 and 0.07, respectively). Among HIV-positive women, HPV-16/18 infection and CD4+ count <200/mm3 were associated with adverse transitions. Conclusions Adverse HIV effects persist throughout HPV natural history stages. Impact In the limited-resource setting of sub-Saharan Africa where cervical cancer screening is not widely available, the high-risk population of HIV-positive women may be ideal for targeted screening. PMID:28515108

Disparity in the persistence of high-risk human papillomavirus genotypes between African American and European American women of college age.

PubMed

Banister, Carolyn E; Messersmith, Amy R; Cai, Bo; Spiryda, Lisa B; Glover, Saundra H; Pirisi, Lucia; Creek, Kim E

2015-01-01

Cervical cancer incidence and mortality rates are higher in African Americans than in European Americans (white, non-Hispanic of European ancestry). The reasons for this disparity are not known. We recruited a population-based longitudinal cohort of 326 European American and 113 African American female college freshmen in Columbia, South Carolina, to compare clearance of high-risk human papillomavirus (HR-HPV) infection between ethnicities. HPV testing and typing from samples obtained for Papanicolaou testing occurred every 6 months. African American participants had an increased risk of testing positive for HR-HPV, compared with European American participants, but the frequency of incident HPV infection was the same in African American and European American women. Thus, exposure to HPV could not explain the higher rate of HPV positivity among African American women. The time required for 50% of participants to clear HR-HPV infection was 601 days for African American women (n = 63) and 316 days for European American women (n = 178; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08-2.53). African American women were more likely than European American women to have an abnormal result of a Papanicolaou test (OR, 1.58; 95% CI, 1.05-2.39). We propose that the longer time to clearance of HR-HPV among African American women leads to increased rates of abnormal results of Papanicolaou tests and contributes to the increased rates of cervical cancer observed in African American women. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Twelve-month trajectories of depressive and anxiety symptoms and associations with traumatic exposure and ongoing adversities: a latent trajectory analysis of a community cohort exposed to severe conflict in Sri Lanka

PubMed Central

Tay, A K; Jayasuriya, R; Jayasuriya, D; Silove, D

2017-01-01

We conducted a 12-month follow-up of a population sample of adults from districts (Mannar, Killinochi, Mullaitivu and Jaffna) exposed to high levels of mass conflict in Sri Lanka, the aim of the present analysis being to identify trajectories of depression and anxiety symptoms and their associations with exposure to psychological trauma and ongoing living adversities. The cohort of 1275 adults (response 86%) followed-up in 2015 was a structured subsample drawn from the baseline nationally representative survey conducted in 2014 across 25 districts in Sri Lanka. Interviews were conducted using electronic tablets by field workers applying contextually adapted indices of trauma exposure, ongoing adversities and symptoms of depression and anxiety. Latent transition analysis revealed a three-class longitudinal model from which four composite trajectories were derived, comprising a persistent symptom trajectory (n=555, 43.5%), an incident or new onset trajectory (n=170, 13.3%), a recovery trajectory (n=299, 23.5%) and a persistently low-symptom trajectory (n=251, 19.7%). Factors associated with both the persistent symptom and incident trajectories were female gender, past trauma exposure and lack of access to health services. Loss of a job was uniquely associated with the persisting trajectory at follow-up. The recovery trajectory comprised a higher proportion of men, older persons and those without risk factors. Our findings assist in translating epidemiologic data into public policy and practice by indicating the importance of stable employment and the provision of healthcare as key factors that may act to reduce anxiety and depressive symptoms in the post-conflict phase. The findings also confirm that women are at high risk of mental distress. Brief screening for trauma exposure in populations with high levels of exposure to mass conflict may assist in defining those at risk of ongoing symptoms of anxiety and depression. PMID:28786977

Persistence: A Key Factor in Human Performance at Work.

ERIC Educational Resources Information Center

Blair, Daniel V.; Price, Donna J.

1998-01-01

Reviews the construct of persistence as it relates to achievement motivation at work. Topics include foundational concepts of persistence; achievement motivation theory; a human motivation model; goal-setting theory; self-efficacy theory; expectancy theory; task assignments; confidence; and perceived value. (LRW)

Chemical Contamination of Green Turtle (Chelonia mydas) Eggs in Peninsular Malaysia: Implications for Conservation and Public Health

PubMed Central

van de Merwe, Jason P.; Hodge, Mary; Olszowy, Henry A.; Whittier, Joan M.; Ibrahim, Kamarruddin; Lee, Shing Y.

2009-01-01

Background Persistent organic pollutants (POPs)—such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)—and heavy metals have been reported in sea turtles at various stages of their life cycle. These chemicals can disrupt development and function of wildlife. Furthermore, in areas such as Peninsular Malaysia, where the human consumption of sea turtle eggs is prevalent, egg contamination may also have public health implications. Objective In the present study we investigated conservation and human health risks associated with the chemical contamination of green turtle (Chelonia mydas) eggs in Peninsular Malaysia. Methods Fifty-five C. mydas eggs were collected from markets in Peninsular Malaysia and analyzed for POPs and heavy metals. We conducted screening risk assessments (SRAs) and calculated the percent of acceptable daily intake (ADI) for POPs and metals to assess conservation and human health risks associated with egg contamination. Results C. mydas eggs were available in 9 of the 33 markets visited. These eggs came from seven nesting areas from as far away as Borneo Malaysia. SRAs indicated a significant risk to embryonic development associated with the observed arsenic concentrations. Furthermore, the concentrations of coplanar PCBs represented 3 300 times the ADI values set by the World Health Organization. Conclusions The concentrations of POPs and heavy metals reported in C. mydas eggs from markets in Peninsular Malaysia pose considerable risks to sea turtle conservation and human health. PMID:19750104

The influence of self-reported leisure time physical activity and the body mass index on recovery from persistent back pain among men and women: a population-based cohort study.

PubMed

Bohman, Tony; Alfredsson, Lars; Hallqvist, Johan; Vingård, Eva; Skillgate, Eva

2013-04-25

There is limited knowledge about leisure time physical activity and the body mass index (BMI) as prognostic factors for recovery from persistent back pain. The aim of this study was to assess the influence of leisure time physical activity and BMI on recovery from persistent back pain among men and women in a general population. The study population (n=1836) in this longitudinal cohort study consisted of participants reporting persistent back pain in the baseline questionnaire in 2002-2003. Data on leisure time physical activity, BMI and potential confounders were also collected at baseline. Information on recovery from persistent back pain (no back pain periods ≥ 7 days during the last 5 years) was obtained from the follow-up questionnaire in 2007. Log-binomial models were applied to calculate Risk Ratios with 95 percent Confidence Intervals (CI) comparing physically active and normal weight groups versus sedentary and overweight groups. Compared to a sedentary leisure time, all measured levels of leisure time physical activity were associated with a greater chance of recovery from persistent back pain among women. The adjusted Risk Ratios was 1.46 (95% CI: 1.06, 2.01) for low leisure time physical activity, 1.51 (95% CI: 1.02, 2.23) for moderate leisure time physical activity, and 1.67 (95% CI: 1.08, 2.58) for high leisure time physical activity. There were no indications that leisure time physical activity influenced recovery among men, or that BMI was associated with recovery from persistent back pain either among men or among women. Regular leisure time physical activity seems to improve recovery from persistent back pain among women.

Human Papillomaviruses and genital co-infections in gynaecological outpatients.

PubMed

Verteramo, Rosita; Pierangeli, Alessandra; Mancini, Emanuela; Calzolari, Ettore; Bucci, Mauro; Osborn, John; Nicosia, Rosa; Chiarini, Fernanda; Antonelli, Guido; Degener, Anna Marta

2009-02-12

High grade HPV infections and persistence are the strongest risk factors for cervical cancer. Nevertheless other genital microorganisms may be involved in the progression of HPV associated lesions. Cervical samples were collected to search for human Papillomavirus (HPV), bacteria and yeast infections in gynaecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods. In this cross-sectional study on 857 enrolled outpatients, statistical analyses revealed a significant association of HPV with C. trachomatis and Ureaplasma urealyticum (at high density) detection, whereas no correlation was found between HPV infection and bacterial vaginosis, Streptococcus agalactiae, yeasts, Trichomonas vaginalis and U. urealyticum. Mycoplasma hominis was isolated only in a few cases both in HPV positive and negative women and no patient was infected with Neisseria gonorrhoeae. Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. A significant association between HPV and C. trachomatis was found and interestingly also with U. urealyticum but only at a high colonization rate. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects.

Human Papillomaviruses and genital co-infections in gynaecological outpatients

PubMed Central

2009-01-01

Background High grade HPV infections and persistence are the strongest risk factors for cervical cancer. Nevertheless other genital microorganisms may be involved in the progression of HPV associated lesions. Methods Cervical samples were collected to search for human Papillomavirus (HPV), bacteria and yeast infections in gynaecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods. Results In this cross-sectional study on 857 enrolled outpatients, statistical analyses revealed a significant association of HPV with C. trachomatis and Ureaplasma urealyticum (at high density) detection, whereas no correlation was found between HPV infection and bacterial vaginosis, Streptococcus agalactiae, yeasts, Trichomonas vaginalis and U. urealyticum. Mycoplasma hominis was isolated only in a few cases both in HPV positive and negative women and no patient was infected with Neisseria gonorrhoeae. Conclusion Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. A significant association between HPV and C. trachomatis was found and interestingly also with U. urealyticum but only at a high colonization rate. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects. PMID:19216747

Persistently active neurons in human medial frontal and medial temporal lobe support working memory

PubMed Central

Kamiński, J; Sullivan, S; Chung, JM; Ross, IB; Mamelak, AN; Rutishauser, U

2017-01-01

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance. PMID:28218914

Brominated flame retardants - Exposure and risk assessment for the general population.

PubMed

Fromme, H; Becher, G; Hilger, B; Völkel, W

2016-01-01

Brominated flame retardants (BFRs) are a large group of different substances used in numerous products to prevent fire hazards. Some of them are persistent in the environment, accumulate in the food chain and are of toxicological concern, while for others current data are limited. Meanwhile, BFRs have been found in many environmental media, foods, and biota including humans. This review presents recent findings obtained from monitoring data in environmental media relevant for human exposure, as well as dietary exposure. In this context, concentrations in indoor and ambient air and in house dust are outlined. Furthermore, we summarize human biomonitoring data on BFR levels in blood and breast milk. Current estimates of the overall exposure of the general population using different relevant subsets are also addressed. All of these data are discussed in relation to currently available toxicological reference values used for risk assessment purposes. Obviously, the exposure of the general population varies considerably in different parts of the world and even within countries. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) show the highest intake during infancy. While the highest intake for BDE 47 for all groups was observed in the US, the total BDE 209 and HBCD intake was highest in the UK. For HBCD and all PBDEs except BDE 209, diet accounts for a large proportion of the total intake during infancy in all countries. With regard to toddlers and adults, the contribution of diet to total intake is high in Germany and the UK, while in the US, the high concentrations of PBDE in dust resulted in a notably smaller proportion of the intake being attributed to diet. Copyright © 2015 Elsevier GmbH. All rights reserved.

Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

PubMed

Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

1991-04-01

A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

Proliferative verrucous leukoplakia: an aggressive form of oral leukoplakia.

PubMed

Shopper, Thomas P; Brannon, Robert B; Stalker, William H

2004-01-01

Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that is persistent, often multifocal, and refractory to treatment with a high risk of recurrence and malignant transformation. This article describes the clinical aspects and histologic features of a case that demonstrated the typical behavior pattern in a long-standing, persistent lesion of PVL of the mandibular gingiva and that ultimately developed into squamous cell carcinoma. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa.

Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda.

PubMed

Respicio-Kingry, Laurel B; Yockey, Brook M; Acayo, Sarah; Kaggwa, John; Apangu, Titus; Kugeler, Kiersten J; Eisen, Rebecca J; Griffith, Kevin S; Mead, Paul S; Schriefer, Martin E; Petersen, Jeannine M

2016-02-01

Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease. During January 2004-December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution. We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk.

Monitoring occurrence and persistence of Listeria monocytogenes in foods and food processing environments in the Republic of Ireland.

PubMed

Leong, Dara; Alvarez-Ordóñez, Avelino; Jordan, Kieran

2014-01-01

Although rates of listeriosis are low in comparison to other foodborne pathogenic illness, listeriosis poses a significant risk to human health as the invasive form can have a mortality rate as high as 30%. Food processors, especially those who produce ready-to-eat (RTE) products, need to be vigilant against Listeria monocytogenes, the causative pathogen of listeriosis, and as such, the occurrence of L. monocytogenes in food and in the food processing environment needs to be carefully monitored. To examine the prevalence and patterns of contamination in food processing facilities in Ireland, 48 food processors submitted 8 samples every 2 months from March 2013 to March 2014 to be analyzed for L. monocytogenes. No positive samples were detected at 38% of the processing facilities tested. Isolates found at the remaining 62% of facilities were characterized by serotyping and Pulsed Field Gel Electrophoresis (PFGE). A general L. monocytogenes prevalence of 4.6% was seen in all samples analyzed with similar rates seen in food and environmental samples. Differences in prevalence were seen across different food processors, food sectors, sampling months etc. and PFGE analysis allowed for the examination of contamination patterns and for the identification of several persistent strains. Seven of the food processing facilities tested showed contamination with persistent strains and evidence of bacterial transfer from the processing environment to food (the same pulsotype found in both) was seen in four of the food processing facilities tested.

Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells.

PubMed

Kortebi, Mounia; Milohanic, Eliane; Mitchell, Gabriel; Péchoux, Christine; Prevost, Marie-Christine; Cossart, Pascale; Bierne, Hélène

2017-11-01

Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious risks to fetuses, newborns and immunocompromised adults. This intracellular bacterial pathogen proliferates in the host cytosol and exploits the host actin polymerization machinery to spread from cell-to-cell and disseminate in the host. Here, we report that during several days of infection in human hepatocytes or trophoblast cells, L. monocytogenes switches from this active motile lifestyle to a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually stopped producing the actin-nucleating protein ActA and became trapped in lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs). Subpopulations of bacteria resisted degradation in LisCVs and entered a slow/non-replicative state. During the subculture of host cells harboring LisCVs, bacteria showed a capacity to cycle between the vacuolar and the actin-based motility stages. When ActA was absent, such as in ΔactA mutants, vacuolar bacteria parasitized host cells in the so-called "viable but non-culturable" state (VBNC), preventing their detection by conventional colony counting methods. The exposure of infected cells to high doses of gentamicin did not trigger the formation of LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results reveal the ability of L. monocytogenes to enter a persistent state in a subset of epithelial cells, which may favor the asymptomatic carriage of this pathogen, lengthen the incubation period of listeriosis, and promote bacterial survival during antibiotic therapy.

Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells

PubMed Central

Mitchell, Gabriel

2017-01-01

Listeria monocytogenes causes listeriosis, a foodborne disease that poses serious risks to fetuses, newborns and immunocompromised adults. This intracellular bacterial pathogen proliferates in the host cytosol and exploits the host actin polymerization machinery to spread from cell-to-cell and disseminate in the host. Here, we report that during several days of infection in human hepatocytes or trophoblast cells, L. monocytogenes switches from this active motile lifestyle to a stage of persistence in vacuoles. Upon intercellular spread, bacteria gradually stopped producing the actin-nucleating protein ActA and became trapped in lysosome-like vacuoles termed Listeria-Containing Vacuoles (LisCVs). Subpopulations of bacteria resisted degradation in LisCVs and entered a slow/non-replicative state. During the subculture of host cells harboring LisCVs, bacteria showed a capacity to cycle between the vacuolar and the actin-based motility stages. When ActA was absent, such as in ΔactA mutants, vacuolar bacteria parasitized host cells in the so-called “viable but non-culturable” state (VBNC), preventing their detection by conventional colony counting methods. The exposure of infected cells to high doses of gentamicin did not trigger the formation of LisCVs, but selected for vacuolar and VBNC bacteria. Together, these results reveal the ability of L. monocytogenes to enter a persistent state in a subset of epithelial cells, which may favor the asymptomatic carriage of this pathogen, lengthen the incubation period of listeriosis, and promote bacterial survival during antibiotic therapy. PMID:29190284