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1.  Associations of mental health problems with waterpipe tobacco and cigarette smoking among college students 
Substance use & misuse  2013;48(3):211-219.
Associations between the emerging trend of waterpipe tobacco smoking and mental health among college students have not been sufficiently explored. This study analyzed data collected from 152 academic institutions that participated in the National College Health Assessment during the 2008–2009 academic year to examine associations between mental health and waterpipe tobacco smoking among college students (N=100,891). For comparison, cigarette smoking was also examined. Associations with mental health variables were very strong for cigarette smoking but only moderate for waterpipe smoking. Study implications and limitations are noted. Funding was provided by NCI Grant [removed for blind version].
doi:10.3109/10826084.2012.750363
PMCID: PMC3582711  PMID: 23302059
Cigarette smoking; College students; Tobacco use; Waterpipe smoking
2.  CD133 expression associated with poor prognosis in ovarian cancer 
As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, at this time its clinical significance in ovarian cancer remains uncertain. The aim of this study was to clarify the clinical role of CD133 expression in human ovarian cancer. Immunohistochemical staining of CD133 expression was performed in 400 ovarian carcinoma samples using tissue microarray. The associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival and disease-free survival time were analyzed. CD133 expression was found in 31% of ovarian carcinoma samples. Fisher’s exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P = 0.035), late-stage disease (P < 0.001), ascites level (P = 0.010), and non-response to chemotherapy (P = 0.023). CD133 expression was also associated with shorter overall survival time (P = 0.007) and shorter disease-free survival time (P < 0.001) by log-rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P = 0.024). Our results thus show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells.
doi:10.1038/modpathol.2011.170
PMCID: PMC3855345  PMID: 22080056
CD133; immunohistochemistry; ovarian cancer; prognosis
3.  Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through defined genetic modifications 
Cell Cycle  2012;11(11):2107-2113.
Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRASV12. Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRASV12-transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTEs can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.
doi:10.4161/cc.20544
PMCID: PMC3368862  PMID: 22592533
fallopian tube epithelial cells; mucinous adenocarcinoma; oncogene; retrovirus; transformation
4.  The Biphasic Role of NF-κB in Progression and Chemoresistance of Ovarian Cancer 
Purpose
NF-κB is a transcription factor known to promote tumorigenesis. However, NF-κB is also known to be proapoptotic and may potentially function as a tumor suppressor, although such a functional role has not been extensively investigated in human cancer.
Experimental Design
A dominant-negative mutant of IκBα with mutations at S32A and S36A was used to inhibit the function of NF-κB in ovarian cancer cell lines. The transcription ability, tumorigenesis, apoptosis, and drug sensitivity were examined in derivative cell lines in comparison with parental cells. We also analyzed the association of nuclear expression of NF-κB p65 with patient survival in an ovarian cancer tissue array.
Results
We show that NF-κB functions as a tumor suppressor in four ovarian cancer cell lines, but it functions as an oncogene in their aggressive chemoresistant isogenic variants. NF-κB can exert its proapoptotic or antiapoptotic effect by activating or repressing mitogen-activated protein kinase (MAPK) phosphorylation in parental or aggressive chemoresistant variant cell lines. We also show that the nuclear accumulation of p65 in epithelial cancer tissue is associated with a good response to chemotherapy and can predict longer overall survival for patients with ovarian cancer.
Conclusions
Our data provide strong evidence that NF-κB can function as a biphasic regulator, either suppressing or enhancing ovarian cancer growth through the regulation of MAPK and cellular apoptosis.
doi:10.1158/1078-0432.CCR-10-3265
PMCID: PMC3152795  PMID: 21339307
5.  Characteristics and consequences of heroin use among older adults in the United States: a review of the literature, treatment implications, and recommendations for further research 
Addictive behaviors  2010;36(4):279-285.
This review reports on the results of a comprehensive literature search of studies examining the physical and mental health characteristics of older adults in the United States who use heroin. Multiple databases were searched for papers meeting the inclusion criteria of heroin users who were age 50 years or older. A total of 14 articles covering 9 different studies met the review inclusion criteria. All of the studies were convenience samples, and seven of the nine studies (77.8%) were entirely drawn from substance abuse treatment programs, primarily methadone maintenance programs. Findings from the qualitative studies suggest that the marginalization of older heroin users was a predominant experience that impacted intent to seek treatment as well as treatment retention. While articles reported high levels of physical and psychological/psychiatric comorbidities with substance misuse, research on heroin use and methadone treatment among older adults is scant and the quantitative findings are inconsistent. The articles reviewed in this study demonstrate that the needs of this population will be significant, yet the development of appropriate interventions and treatment for older adult heroin users will be contingent on empirical research that adequately describes mental and physical health problems.
doi:10.1016/j.addbeh.2010.12.012
PMCID: PMC3127414  PMID: 21237575
Heroin; methadone maintenance treatment; mental health disorders; physical health problems
6.  AURKA and BRCA2 expression highly correlate with prognosis of endometriofid ovarian carcinoma 
Aurora kinase A (AURKA), a serine/threonine kinase, has been shown to regulate the cell cycle checkpoint and maintain genomic integrity. AURKA is overexpressed in various carcinomas. Breast cancer 2, early onset (BRCA2) has an important role in maintaining genomic stability and acts as a tumor suppressor. Our recent study suggested that AURKA regulates genomic instability and tumorigenesis through cell cycle dysregulation and suppression of BRCA2 expression. However, the expression of AURKA, BRCA2 and their clinical significance is unknown in endometrioid ovarian cancer. In this study, we determined AURKA and BRCA2 expression in endometrioid ovarian carcinoma and correlated them with clinicopathologic characteristics and patient survival. Immunohistochemical staining was performed in 51 primary endometrioid ovarian carcinoma tumor samples, using tissue microarray. We then analyzed the associations between AURKA and BRCA2 expression and clinical factors (tumor grade, disease stage, surgical type, clinical response, and relapse) and overall and disease-free survival durations. AURKA and BRCA2 expression were found in 48 and 29% of the samples, respectively. The results of Fisher’s exact test suggested that AURKA expression was significantly associated with no family history of ovarian cancer (P=0.03) and that BRCA2 expression was associated with early-stage disease (P=0.03), low ascites incidence (P=0.03), younger age (<60) at diagnosis (P=0.03), and low-grade tumors (P<0.01). The nuclear BRCA2 score was negatively correlated with AURKA score (P=0.019, two-tailed Pearson correlation). A log-rank test demonstrated that AURKA expression was associated with shorter overall (P=0.001) and disease-free (P=0.009) survival durations, and that BRCA2 expression was associated with longer overall (P=0.000) and disease-free (P=0.002) durations. Patients with BRCA2-positive and AURKA-negative tumors had higher overall (P=0.001) and disease-free (P=0.001) survival rates than did patients with AURKA-positive and BRCA2-negative tumors. Our results demonstrate that a negative regulatory loop exists between AURKA and BRCA2 expression in the ovarian endometrioid carcinoma. AURKA expression is an unfavorable prognostic factor in patients with endometrioid ovarian cancer and BRCA2 is favorable, combination of these two markers may better predict the prognosis of patients with endometrioid ovarian carcinoma than individual marker alone.
doi:10.1038/modpathol.2011.44
PMCID: PMC3152794  PMID: 21441901
AURKA; BRCA2; endometrioid ovarian carcinoma; prognostic factors
7.  CXCR2 Promotes Ovarian Cancer Growth through Dysregulated Cell Cycle, Diminished Apoptosis, and Enhanced Angiogenesis 
Purpose
Chemokine receptor CXCR2 is associated with malignancy in several cancer models; however, the mechanisms involved in CXCR2-mediated tumor growth remain elusive. Here, we investigated the role of CXCR2 in human ovarian cancer.
Experimental Design
CXCR2 expression was silenced by stable small hairpin RNA in ovarian cancer cell lines T29Gro-1, T29H, and SKOV3. Western blotting, immunofluorescence, enzyme-linked immunosorbent assay, flow cytometry, electrophoretic mobility shift assay, and mouse assay were used to detect CXCR2, interleukin-8, Gro-1, cell cycle, apoptosis, DNA binding of NF-κB, and tumor growth. Immunohistochemical staining of CXCR2 was done in 240 high-grade serous ovarian carcinoma samples.
Results
Knockdown of CXCR2 expression by small hairpin RNA reduced tumorigenesis of ovarian cancer cells in nude mice. CXCR2 promoted cell cycle progression by modulating cell cycle regulatory proteins, including p21 (waf1/cip1), cyclin D1, CDK6, CDK4, cyclin A, and cyclin B1. CXCR2 inhibited cellular apoptosis by suppressing phosphorylated p53, Puma, and Bcl-xS; suppressing poly(ADP-ribose) polymerase cleavage; and activating Bcl-xL and Bcl-2. CXCR2 stimulated angiogenesis by increasing levels of vascular endothelial growth factor and decreasing levels of thrombospondin-1, a process likely involving mitogen-activated protein kinase, and NF-κB. Overexpression of CXCR2 in high-grade serous ovarian carcinomas was an independent prognostic factor of poor overall survival (P < 0.001) and of early relapse (P = 0.003) in the univariate analysis.
Conclusions
Our data provide strong evidence that CXCR2 regulates the cell cycle, apoptosis, and angiogenesis through multiple signaling pathways, including mitogen-activated protein kinase and NF-κB, in ovarian cancer. CXCR2 thus has potential as a therapeutic target and for use in ovarian cancer diagnosis and prognosis.
doi:10.1158/1078-0432.CCR-10-0483
PMCID: PMC2930833  PMID: 20505188
8.  Adapting problem-solving therapy for depressed older adults in methadone maintenance treatment 
Late life depression is prevalent in older adults who are dependent on opiates. Depressive disorders among opiate abusers have detrimental effects on their well-being and ability to refrain from illegal drugs. There are numerous barriers to the provision of appropriate mental health care to older adults receiving methadone maintenance treatment. This article focuses on problem solving therapy (PST) and presents evidence that PST may be a promising non-pharmacological treatment for older methadone clients with comorbid depressive disorders that can be applied within the staffing and resource limits of methadone maintenance treatment facilities. The advantages of PST relative to other behavioral therapies for this population are based on evidence that PST is less cognitively demanding for an older adult population with mood and substance use disorders. A properly modified PST for an older adult substance dependent population with subsyndromal or diagnosed depression may be a viable option for methadone maintenance programs with limited resources.
doi:10.1016/j.jsat.2010.09.003
PMCID: PMC3142774  PMID: 21036509
9.  Mental Health Treatment Seeking Among Older Adults with Depression: The Impact of Stigma and Race 
Objective
Stigma associated with mental illness continues to be a significant barrier to help seeking, leading to negative attitudes about mental health treatment and deterring individuals who need services from seeking care. This study examined the impact of public stigma (negative attitudes held by the public) and internalized stigma (negative attitudes held by stigmatized individuals about themselves) on racial differences in treatment seeking attitudes and behaviors among older adults with depression.
Method
Random digit dialing was utilized to identify a representative sample of 248 African American and White adults older adults (over the age of 60) with depression (symptoms assessed via the Patient Health Questionnaire-9). Telephone based surveys were conducted to assess their treatment seeking attitudes and behaviors, and the factors that impacted these behaviors.
Results
Depressed older adult participants endorsed a high level of public stigma and were not likely to be currently engaged in, nor did they intend to seek mental health treatment. Results also suggested that African American older adults were more likely to internalize stigma and endorsed less positive attitudes toward seeking mental health treatment than their White counterparts. Multiple regression analysis indicated that internalized stigma partially mediated the relationship between race and attitudes toward treatment.
Conclusion
Stigma associated with having a mental illness has a negative influence on attitudes and intentions toward seeking mental health services among older adults with depression, particularly African American elders. Interventions to target internalized stigma are needed to help engage this population in psychosocial mental health treatments.
doi:10.1097/JGP.0b013e3181cc0366
PMCID: PMC2875324  PMID: 20220602
Stigma; Depression; Treatment; Aging
10.  Exploring the reasons urban and rural-dwelling older adults participate in memory research 
This study examines how underrepresented older urban and rural-dwelling individuals conceptualize participation in cognitive impairment studies. Nine focus groups were held with urban and rural-dwelling older adults who had participated in a community-based memory screening study. Expected and experienced benefits of research participation were motivators for study participation in all focus groups. Results indicate that participation in memory research was believed to lead to an understanding of memory function. Focus group participants expressed an active interest in research on dementia, and viewed research participation as a way to address memory concerns and provide a benefit to society.
doi:10.1177/1533317511399569
PMCID: PMC3088766  PMID: 21343152
underrepresented older adults; research participation; dementia; mild cognitive impairment; focus groups
11.  Correlation of Tissue Biopsy and Fine Needle Aspiration Cytology with Positron Emission Tomography Results 
F-18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans are positive in any condition which increases metabolism in a mass or tissue and are therefore not specific for neoplastic conditions. The use of an SUV cutoff value of 2.5 may not always help discriminate between benign and malignant cases. For a practicing cytopathologist doing adequacy checks during an image-guided procedure, it may be of value to be aware that elevated SUV values are not always indicative of a malignant process, and vice versa.
doi:10.4061/2011/323051
PMCID: PMC3090089  PMID: 21559200
12.  Barriers to treatment and culturally endorsed coping strategies among depressed African-American older adults 
Aging & mental health  2010;14(8):971-983.
Objective
Older adults are particularly vulnerable to the effects of depression, however, they are less likely to seek and engage in mental health treatment. African-American older adults are even less likely than their White counterparts to seek and engage in mental health treatment. This qualitative study examined the experience of being depressed among African-American elders and their perceptions of barriers confronted when contemplating seeking mental health services. In addition, we examined how coping strategies are utilized by African-American elders who choose not to seek professional mental health services.
Method
A total of 37 interviews were conducted with African-American elders endorsing at least mild symptoms of depression. Interviews were audiotaped and subsequently transcribed. Content analysis was utilized to analyze the qualitative data.
Results
Thematic analysis of the interviews with African-American older adults is presented within three areas: (1) Beliefs about Depression Among Older African-Americans: (2) Barriers to Seeking Treatment for Older African-Americans: and (3) Cultural Coping Strategies for Depressed African-American Older Adults.
Conclusion
Older African-Americans in this study identified a number of experiences living in the Black community that impacted their treatment seeking attitudes and behaviors. which led to identification and utilization of more culturally endorsed coping strategies to deal with their depression. Findings from this study provide a greater understanding of the stigma associated with having a mental illness and its influence on attitudes toward mental health services.
doi:10.1080/13607863.2010.501061
PMCID: PMC3060025  PMID: 21069603
depression; beliefs/attitudes; health service use; stigma; aging
13.  Significance of Travel to Rural Areas as a Risk Factor for Malarial Anemia in an Urban Setting 
The epidemiology of malaria in urban environments is poorly characterized, yet increasingly problematic. We conducted an unmatched case–control study of risk factors for malarial anemia with high parasitemia in urban Kisumu, Kenya, from June 2002 through February 2003. Cases (n = 80) were hospital patients with a hemoglobin level ≤ 8 g/dL and a Plasmodium parasite density ≥ 10,000/μL. Controls (n = 826) were healthy respondents to a concurrent citywide knowledge, attitude, and practice survey. Children who reported spending at least one night per month in a rural area were especially at risk (35% of cases; odds ratio = 9.3, 95% confidence interval [CI] = 4.4–19.7, P < 0.0001), and use of mosquito coils, bed net ownership, and house construction were non-significant, potentially indicating that malaria exposure during rural travel comprises an important element of risk. Control of severe malaria in an urban setting may be complicated by Plasmodium infections acquired elsewhere. Epidemiologic studies of urban malaria in low transmission settings should take travel history into account.
doi:10.4269/ajtmh.2010.09-0047
PMCID: PMC2829898  PMID: 20207862
14.  Diabetes Surgery: A New Approach to an Old Disease 
Diabetes Care  2009;32(Suppl 2):S368-S372.
doi:10.2337/dc09-S341
PMCID: PMC2811475  PMID: 19875583
15.  Induction of papillary carcinoma in human ovarian surface epithelial cells using combined genetic elements and peritoneal microenvironment 
Cell cycle (Georgetown, Tex.)  2010;9(1):140-146.
Papillary differentiation is one of the most common histological features of ovarian cancer, although the underlying mechanism that leads to such differentiation is not known. We hypothesized that human ovarian surface epithelial cells can be transformed into carcinoma with papillary differentiation by overexpressing HER2/neu in these cells. Mice were injected either subcutaneously or intraperitoneally with two immortalized human ovarian surface epithelial cell lines after enforced expression of HER-2/neu. Mice subcutaneously injected with tumor cells from either the T29Nt or T80Nt developed undifferentiated carcinomas. In contrast, mice injected intraperitoneally with T29Nt cells developed papillary carcinoma, and those injected intraperitoneally with T80Nt cells developed undifferentiated carcinoma. Our results demonstrate that ovarian surface epithelial cells can develop into papillary carcinoma in mice, and that the induction of papillary differentiation depends not only on specific genetic modifications but also on the tumor microenvironment and epithelial cell type from ovary from different patients.
PMCID: PMC2931318  PMID: 20016289
high grade serous carcinoma; HER2/neu; human ovarian surface epithelial cells; transformation
16.  Morphological and molecular basis of ovarian serous carcinoma 
Journal of Biomedical Research  2010;24(4):257-263.
Serous carcinoma is the most common type of epithelial ovarian cancer. In this review, we provide a comprehensive picture of ovarian serous cancers from multiple aspects: the first part of this review summarizes the morphological, histological, and immunological signatures of ovarian serous carcinoma; subsequently, we review the history of the evolvement of different grading systems used in ovarian serous cancer; in the end, we focus on characterizing the genetics that underlie the 2-tiered pathways through which ovarian serous cancers are believed to arise: the low-grade and the high-grade pathways.
doi:10.1016/S1674-8301(10)60036-X
PMCID: PMC3596590  PMID: 23554638
ovarian carcinoma; grading; morphology; molecular genetics; tumorigenesis
17.  Cerebral Sinus Thrombosis: A Fatal Neurological Complication of Ulcerative Colitis 
Cerebral sinus thrombosis has been reported as an uncommon complication of ulcerative colitis (UC), occurring in up to 7.5% of cases. It is suspected to be a consequence of genetic predisposition and the hypercoagulable state occurring during disease relapse. We report a case of a 23-year-old male patient with one-year history of UC. He presented to the Emergency Room with left-sided progressive hemiparesis, numbness, hemiparesthesia, and pain, which followed a recent exacerbation of UC. The patient died 3 days after admission and an autopsy revealed superior and inferior sagittal sinus and cortical vein thrombosis with associated cerebral edema, hemorrhagic infarction, and herniation. The gastrointestinal tract had continuous cobblestone appearance extending from rectum to cecum, with hemorrhage and ulceration, consistent with active UC. Awareness of this rare complication of UC can contribute to early recognition and attempts at treatment of this serious and often fatal condition.
doi:10.4061/2010/132754
PMCID: PMC2997282  PMID: 21152173
18.  Ovarian cancer: pathology, biology, and disease models 
Epithelial ovarian cancer, which comprises several histologic types and grades, is the most lethal cancer among women in the United States. In this review, we summarize recent progress in understanding the pathology and biology of this disease and in development of models for preclinical research. Our new understanding of this disease suggests new targets for therapeutic intervention and novel markers for early detection of disease.
PMCID: PMC2858969  PMID: 19273186
Ovarian cancer; Pathology; Senescence; Disease Models; Review
19.  ALDH1 Expression Correlates with Favorable Prognosis in Ovarian Cancers 
Aldehyde dehydrogenase 1 (ALDH1), a detoxifying enzyme responsible for the oxidation of intracellular aldehydes, was shown to play a role in the early differentiation of stem cells, through its role in oxidizing retinol to retinoic acid. It has been shown that ALDH1 is a predictor of poor clinical outcome in breast cancer. The authors hypothesized that the level of ALDH1 expression may be correlated with the clinical outcome of patients with ovarian cancer. Immunohistochemical staining of ALDH1 expression was analyzed in 442 primary ovarian carcinomas using tissue microarray. The associations between the expression of the ALDH1 and clinical factors (diagnosis, tumor grade, stage, and clinical response to chemotherapy), as well overall and disease-free survival were analyzed. Expression of ALDH1 was found in 48.9% of the samples. Fisher's exact test suggested that high expression of ALDH1 was significantly associated with endometrioid adenocarcinoma (P < 0.0001), early-stage disease (P = 0.006), complete response to chemotherapy (P <0.05) and a low serum level of CA125 (P = 0.02). High percentage of cells expressing ALDH1 was associated with a longer overall survival time (P =0.01) and disease free survival time (P = 0.006) by Log rank test. In contrast to its role in breast cancer, ALDH1 was a favorable prognostic factor in ovarian carcinoma. ALDH1 therefore may play a different role in ovarian cancer than it does in breast cancer.
doi:10.1038/modpathol.2009.35
PMCID: PMC2692456  PMID: 19329942
ALDH1; Ovarian Cancer; Immunohistochemistry; Prognosis
20.  PEA-15 Induces Autophagy in Human Ovarian Cancer Cells and is Associated with Prolonged Overall Survival 
Cancer research  2008;68(22):9302-9310.
Phospho-enriched protein in astrocytes (PEA-15) is a 15-kDa phosphoprotein that slows cell proliferation by binding to and sequestering extracellular signal-regulated kinase (ERK) in the cytoplasm, thereby inhibiting ERK-dependent transcription and proliferation. In previous studies of E1A human gene therapy for ovarian cancer, we discovered that PEA-15 induced the antitumor effect of E1A by sequestering activated ERK in the cytoplasm of cancer cells. Here, we investigated the role of PEA-15 in ovarian cancer tumorigenesis, the expression levels of PEA-15 in human ovarian cancer, and whether PEA-15 expression correlated with overall survival in women with ovarian cancer. We overexpressed PEA-15 in low-PEA-15-expressing cells and knocked down PEA-15 in high-PEA-15-expressing cells and analyzed the effect on proliferation, anchorage-independent growth, and cell cycle progression. We then assessed PEA-15 expression in an annotated tissue microarray of tumor samples from 395 women with primary epithelial ovarian cancer and tested whether PEA-15 expression was linked with overall survival. PEA-15 expression inhibited proliferation, and cell cycle analysis did not reveal apoptosis but did reveal autophagy, which was confirmed by an increase in LC3 cleavage. Inhibition of the ERK1/2 pathway decreased PEA-15-induced autophagy. These findings suggested that the antitumor activity of PEA-15 is mediated in part by the induction of autophagy involving activation of the ERK1/2 pathway. Multivariable analyses indicated that the women with high-PEA-15-expressing tumors survived longer than those with low-PEA-15-expressing tumors (hazard ratio = 1.973, P = 0.0167). Our findings indicate that PEA-15 expression is an important prognostic marker in ovarian cancer.
doi:10.1158/0008-5472.CAN-08-2592
PMCID: PMC2676677  PMID: 19010903
survival; autophagy; ovarian neoplasms; PEA-15; ERK
21.  Identification of a chemical probe for NAADP by virtual screening 
Nature chemical biology  2009;5(4):220-226.
Research into the biological role of the Ca2+-releasing second messenger NAADP (nicotinic acid adenine dinucleotide phosphate) has been hampered by a lack of chemical probes. To find new chemical probes for exploring NAADP signaling, we turned to virtual screening, which can evaluate millions of molecules rapidly and inexpensively. We used NAADP as the query ligand to screen the chemical library ZINC for compounds with 3D-shape and electrostatic similarity. We tested the top-ranking hits in a sea urchin egg bioassay and found that one hit, Ned-19, blocks NAADP signaling at nanomolar concentrations. In intact cells, Ned-19 blocked NAADP signaling and fluorescently labeled NAADP receptors. Moreover, we show the utility of Ned-19 as a chemical probe by using it to demonstrate that NAADP is a key causal link between glucose sensing and Ca2+ increases in mouse pancreatic beta cells.
doi:10.1038/nchembio.150
PMCID: PMC2659327  PMID: 19234453
22.  Geohelminth Infections among Pregnant Women in Rural Western Kenya; a Cross-Sectional Study 
Background
Geohelminth infections are common in rural western Kenya, but risk factors and effects among pregnant women are not clear.
Methodology
During a community-based cross-sectional survey, pregnant women were interviewed and asked to provide a blood sample and a single fecal sample. Hemoglobin was measured and a blood slide examined for malaria. Geohelminth infections were identified using the concentration and Kato-Katz method.
Results
Among 390 participants who provided a stool sample, 76.2% were infected with at least one geohelminth: 52.3% with Ascaris lumbricoides, 39.5% with hookworm, and 29.0% with Trichuris trichiura. Infection with at least one geohelminth species was associated with the use of an unprotected water source (adjusted odds ratio [AOR] 1.8, 95% confidence interval [CI] 1.1–3.0) and the lack of treatment of drinking water (AOR 1.8, 95% CI 1.1–3.1). Geohelminth infections were not associated with clinical symptoms, or low body mass index. A hookworm infection was associated with a lower mid upper arm circumference (adjusted mean decrease 0.7 cm, 95% CI 0.3–1.2 cm). Hookworm infections with an egg count ≥1000/gram feces (11 women) were associated with lower hemoglobin (adjusted mean decrease 1.5 g/dl, 95% CI 0.3–2.7). Among gravidae 2 and 3, women with A. lumbricoides were less likely to have malaria parasitemia (OR 0.4, 95% CI 0.2–0.8) compared to women without A. lumbricoides, unlike other gravidity groups.
Conclusion
Geohelminth infections are common in this pregnant population; however, there were few observed detrimental effects. Routine provision of antihelminth treatment during an antenatal clinic visit is recommended, but in this area an evaluation of the impact on pregnancy, malaria, and birth outcome is useful.
Author Summary
In rural western Kenya, both malaria and intestinal infections with worms are common. Pregnant women are particularly vulnerable to infection with malaria, but the effect on pregnancy of intestinal infections with worms is not clear and may depend both on how heavy the worm infection is and on the type of worm. Additionally, it is not clear whether infections with worms may affect malaria infections. In this article, we begin to disentangle some of these issues. Intestinal infections with worms were diagnosed in three-quarters of 390 pregnant women in western Kenya who provided a stool sample. In these women, intestinal worm infections caused a modest decrease both in haemoglobin levels and indicators of nutritional status. Women in their second and third pregnancies who were diagnosed with one particular type of worm infection (Ascaris lumbricoides) were less likely to have malaria than other women in their second or third pregnancies who did not have this type of worm infection. Although our results suggest that it would be good advice to treat women with drugs for intestinal worm infections during their pregnancy in this area, the effect on maternal and infant health and malaria infection needs further study.
doi:10.1371/journal.pntd.0000370
PMCID: PMC2627942  PMID: 19172184
23.  Reproductive health issues in rural Western Kenya 
Background
We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%).
Methods
We conducted a community-based cross-sectional survey among rural pregnant women in western Kenya. A medical, obstetric and reproductive history was obtained. Blood was obtained for a malaria smear and haemoglobin level, and stool was examined for geohelminths. Height and weight were measured.
Results
Of 673 participants, 87% were multigravidae and 50% were in their third trimester; 41% had started antenatal clinic visits at the time of interview and 69% reported ITN-use. Malaria parasitemia and anaemia (haemoglobin < 11 g/dl) were detected among 36% and 53% of the women, respectively. Geohelminth infections were detected among 76% of the 390 women who gave a stool sample. Twenty percent of women were underweight, and sixteen percent reported symptoms of herpes zoster or oral thrush in the last two months. Nineteen percent of all women reported using a contraceptive method to delay or prevent pregnancy before the current pregnancy (injection 10%, pill 8%, condom 0.4%). Twenty-three percent of multigravidae conceived their current pregnancy within a year of the previous pregnancy. More than half of the multigravidae (55%) had ever lost a live born child and 21% had lost their last singleton live born child at the time of interview.
Conclusion
In this rural area with a high HIV prevalence, the reported use of condoms before pregnancy was extremely low. Pregnancy health was not optimal with a high prevalence of malaria, geohelminth infections, anaemia and underweight. Chances of losing a child after birth were high. Multiple interventions are needed to improve reproductive health in this area.
doi:10.1186/1742-4755-5-1
PMCID: PMC2291034  PMID: 18348726
24.  A census-weighted, spatially-stratified household sampling strategy for urban malaria epidemiology 
Malaria Journal  2008;7:39.
Background
Urban malaria is likely to become increasingly important as a consequence of the growing proportion of Africans living in cities. A novel sampling strategy was developed for urban areas to generate a sample simultaneously representative of population and inhabited environments. Such a strategy should facilitate analysis of important epidemiological relationships in this ecological context.
Methods
Census maps and summary data for Kisumu, Kenya, were used to create a pseudo-sampling frame using the geographic coordinates of census-sampled structures. For every enumeration area (EA) designated as urban by the census (n = 535), a sample of structures equal to one-tenth the number of households was selected. In EAs designated as rural (n = 32), a geographically random sample totalling one-tenth the number of households was selected from a grid of points at 100 m intervals. The selected samples were cross-referenced to a geographic information system, and coordinates transferred to handheld global positioning units. Interviewers found the closest eligible household to the sampling point and interviewed the caregiver of a child aged < 10 years. The demographics of the selected sample were compared with results from the Kenya Demographic and Health Survey to assess sample validity. Results were also compared among urban and rural EAs.
Results
4,336 interviews were completed in 473 of the 567 study area EAs from June 2002 through February 2003. EAs without completed interviews were randomly distributed, and non-response was approximately 2%. Mean distance from the assigned sampling point to the completed interview was 74.6 m, and was significantly less in urban than rural EAs, even when controlling for number of households. The selected sample had significantly more children and females of childbearing age than the general population, and fewer older individuals.
Conclusion
This method selected a sample that was simultaneously population-representative and inclusive of important environmental variation. The use of a pseudo-sampling frame and pre-programmed handheld GPS units is more efficient and may yield a more complete sample than traditional methods, and is less expensive than complete population enumeration.
doi:10.1186/1475-2875-7-39
PMCID: PMC2292736  PMID: 18312632
25.  Quantitative urban classification for malaria epidemiology in sub-Saharan Africa 
Malaria Journal  2008;7:34.
Background
Although sub-Saharan Africa (SSA) is rapidly urbanizing, the terms used to classify urban ecotypes are poorly defined in the context of malaria epidemiology. Lack of clear definitions may cause misclassification error, which likely decreases the accuracy of continent-wide estimates of malaria burden, limits the generalizability of urban malaria studies, and makes identification of high-risk areas for targeted interventions within cities more difficult. Accordingly, clustering techniques were applied to a set of urbanization- and malaria-related variables in Kisumu, Kenya, to produce a quantitative classification of the urban environment for malaria research.
Methods
Seven variables with a known or expected relationship with malaria in the context of urbanization were identified and measured at the census enumeration area (EA) level, using three sources: a) the results of a citywide knowledge, attitudes and practices (KAP) survey; b) a high-resolution multispectral satellite image; and c) national census data. Principal components analysis (PCA) was used to identify three factors explaining higher proportions of the combined variance than the original variables. A k-means clustering algorithm was applied to the EA-level factor scores to assign EAs to one of three categories: "urban," "peri-urban," or "semi-rural." The results were compared with classifications derived from two other approaches: a) administrative designation of urban/rural by the census or b) population density thresholds.
Results
Urban zones resulting from the clustering algorithm were more geographically coherent than those delineated by population density. Clustering distributed population more evenly among zones than either of the other methods and more accurately predicted variation in other variables related to urbanization, but not used for classification.
Conclusion
Effective urban malaria epidemiology and control would benefit from quantitative methods to identify and characterize urban areas. Cluster analysis techniques were used to classify Kisumu, Kenya, into levels of urbanization in a repeatable and unbiased manner, an approach that should permit more relevant comparisons among and within urban areas. To the extent that these divisions predict meaningful intra-urban differences in malaria epidemiology, they should inform targeted urban malaria interventions in cities across SSA.
doi:10.1186/1475-2875-7-34
PMCID: PMC2277427  PMID: 18298857

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