HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

PURPOSE: For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. METHODS: Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. RESULTS: Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. CONCLUSIONS: Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Pilot and feasibility study: prospective proteomic profiling of mammary epithelial cells from high-risk women provides evidence of activation of pro-survival pathways.

Normal mammary gland homeostasis requires the coordinated regulation of protein signaling networks. However, we have little prospective information on whether activation of protein signaling occurs in premalignant mammary epithelial cells, as represented by cells with cytological atypia from women who are at high risk for breast cancer. This information is critical for understanding the role of deregulated signaling pathways in the initiation of breast cancer and for developing targeted prevention and/or treatment strategies for breast cancer in the future. In this pilot and feasibility study, we examined the expression of 52 phosphorylated, total, and cleaved proteins in 31 microdissected Random Periareolar Fine Needle Aspiration (RPFNA) samples by high-throughput Reverse Phase Protein Microarray. Unsupervised hierarchical clustering analysis indicated the presence of four clusters of proteins that represent the following signaling pathways: (1) receptor tyrosine kinase/Akt/mammalian target of rapamycin (RTK/Akt/mTOR), (2) RTK/Akt/extracellular signal-regulated kinase (RTK/Akt/ERK), (3) mitochondrial apoptosis, and (4) indeterminate. Clusters 1 through 3 comprised moderately to highly expressed proteins, while Cluster 4 comprised proteins that are lowly expressed in a majority of RPFNA samples. Our exploratory study showed that the interlinked components of mitochondrial apoptosis pathway are highly expressed in all mammary epithelial cells obtained from high-risk women. In particular, the expression levels of anti-apoptotic Bcl-xL and pro-apoptotic Bad are positively correlated in both non-atypical and atypical samples (unadjusted P < 0.0001), suggesting a delicate balance between the pro-apoptotic and anti-apoptotic regulation of cell proliferation during the early steps of mammary carcinogenesis. Our feasibility study suggests that the activation of key proteins along the RTK/Akt pathway may tip this balance to cell survival. Taken together, our results demonstrate the feasibility of mapping proteomic signaling networks in limited RPFNA samples obtained from high-risk women and the promise of developing rational drug targets or preventative strategies for breast cancer in future proteomic studies with a larger cohort of high-risk women.

Venous Thromboembolism Prophylaxis and Hormonal Contraceptive Management Practice Patterns in the Perioperative Period for Anterior Cruciate Ligament Reconstruction.

Purpose: To evaluate the venous thromboembolism (VTE) prophylaxis practices of surgeons performing anterior cruciate ligament reconstruction (ACLR) in female patients using hormonal contraceptives. Methods: Our research team designed an investigational survey using branching logic that was made available to the AANA membership. The survey was designed to identify clinical decision making regarding VTE prophylaxis after ACLR in patients without risk factors for VTE, the counseling of patients about VTE risk associated with hormonal contraceptives, and the use of VTE prophylaxis after ACLR in patients taking hormonal contraceptives. Results: Ninety-four respondents completed the survey. Eighty-nine respondents identified their gender (63% male and 37% female respondents). Respondents reported performing the following number of ACLRs annually: more than 50 (40%), 30 to 50 (29%), 15 to 30 (29%), and fewer than 15 (2%). Of the respondents, 62 (67%) reported that VTE developed after ACLR in their patients (male patients only, 32%; female patients only, 24%; and both male and female patients, 34%). Sixty-seven percent used chemoprophylaxis after ACLR. Surgeons who asked about hormonal contraceptive use were more likely to be women (P = .01; odds ratio [OR], 4.2). Surgeons who changed their VTE prophylaxis plan as a result of asking about hormonal contraceptive use were more likely to be women (P = .02; OR, 2.8). Surgeons who asked about hormonal contraceptive use were more likely to have female patients with VTE after ACLR (P = .03; OR, 2.9). Surgeons who changed their VTE prophylaxis plan as a result of asking about hormonal contraceptive use were more likely to have female patients with VTE after ACLR (P = .001; OR, 4.6). Conclusions: There is no standard of care for VTE prophylaxis after ACLR. A surgeon's own gender and prior clinical experience with VTE after ACLR may influence his or her likelihood to consider a patient's hormonal contraceptive use regarding VTE risk after ACLR. Clinical Relevance: The use of hormonal contraception is a risk factor for VTE in female patients undergoing ACLR. It is important to identify current practice patterns and the need for a standard of care.

Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.

BACKGROUND: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. METHODS: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. RESULTS: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36). CONCLUSIONS: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy.

OBJECTIVE: The aim of the study was to review the role of hormone therapy in menopausal patients with breast cancer and gynecologic malignancies. METHODS: We searched MEDLINE (via PubMed) using a combination of keywords and database-specific subject headings for the following concepts: menopause, hormone therapy, and cancer. Editorials, letters, case reports, and comments were excluded, as were non-English articles. Additional references were identified by hand-searching bibliographies of included articles. The searches yielded a total of 1,484 citations. All citations were imported into EndNote X9, where they were screened by the authors. RESULTS: In breast cancer survivors, systemic hormone therapy is not recommended, whereas local low-dose estrogen therapy may be considered after discussion with the patient's oncologist. Among endometrial cancer survivors, hormone therapy is considered safe in low-risk cancers but should be avoided in high-risk subtypes. For survivors of epithelial ovarian cancer and cervical cancer, hormone therapy can be considered, but should be avoided in women with estrogen-sensitive histologic subtypes. CONCLUSIONS: The risks of hormone therapy should be assessed on an individual basis, with consideration of age, type of hormone therapy, dose, duration of use, regimen, route, and prior exposure. Systemic hormone therapy is not recommended in breast cancer survivors, whereas vaginal low-dose estrogen appears safe. Hormone therapy may be used by endometrial, cervical, and ovarian cancer survivors with low-risk, non-estrogen-receptor-positive subtypes. Video Summary: http://links.lww.com/MENO/A516.

Emergence of a Neolithic in highland New Guinea by 5000 to 4000 years ago.

The emergence of agriculture was one of the most notable behavioral transformations in human history, driving innovations in technologies and settlement globally, referred to as the Neolithic. Wetland agriculture originated in the New Guinea highlands during the mid-Holocene (8000 to 4000 years ago), yet it is unclear if there was associated behavioral change. Here, we report the earliest figurative stone carving and formally manufactured pestles in Oceania, dating to 5050 to 4200 years ago. These discoveries, at the highland site of Waim, occur with the earliest planilateral axe-adzes in New Guinea, the first evidence for fibercraft, and interisland obsidian transfer. The combination of symbolic social systems, complex technologies, and highland agricultural intensification supports an independent emergence of a Neolithic ~1000 years before the arrival of Neolithic migrants (Lapita) from Southeast Asia.

Acupuncture in Obstetrics and Gynecology.

IMPORTANCE: Acupuncture is a key component of therapy in traditional Chinese medicine. Only in the last few decades has acupuncture become popular in the United States. The mechanism behind acupuncture's effects on the body and brain has not been completely elucidated, but there is evidence that acupuncture has effects on the endocrine, immune, and sympathetic and parasympathetic nervous systems. It may also act through electrical and mechanical signaling through the connective tissue and fascia. Despite this uncertainty, the positive effects of acupuncture have been well established. OBJECTIVE: In this review, we discuss the basic concepts of traditional Chinese medicine and acupuncture and examine the evidence regarding the use of acupuncture in obstetrics and gynecology. EVIDENCE ACQUISITION: We conducted a literature review of acupuncture in obstetrics and gynecology using PubMed. RESULTS: The available data demonstrate that acupuncture is beneficial in the treatment of labor pain, back pain in pregnancy, and dysmenorrhea. It is unclear if acupuncture is effective for hyperemesis, chemotherapy-induced nausea and vomiting, and menopausal hot flushes, or if moxibustion is effective in correcting breech presentation. There are limited but positive data regarding menopause-related sleep disturbances, depression in pregnancy, and overactive bladder. Acupuncture is not beneficial for improving outcomes in in vitro fertilization. CONCLUSIONS AND RELEVANCE: Acupuncture is an increasingly popular therapy with many potential applications in obstetrics and gynecology. A general understanding of the basic principles of acupuncture and the safety and efficacy of its practice is necessary for the general obstetrician and gynecologist to make informed recommendations to patients.

A Critique of Risk Disclosure as the Solution for Minimizing Toxic Exposures in Pregnancy.

The issue of pregnant women's exposures to everyday chemicals and the implications for the health of future children are receiving increased attention in popular media and in the academic press. In response, health profession organizations are developing clinical practice guidelines for warning pregnant women about the risks associated with exposures to certain toxics. We evaluate different sides of a risk-avoidance approach for pregnant women in the context of a hypothetical case study involving phthalates and women who work in nail salons. We consider the ubiquitous nature of low-dose exposures and both the positive aspects and limitations of promoting avoidance measures with respect to phthalate exposures. We conclude that a risk-disclosure approach has both practical limitations and equity dimensions which must be factored in to public health guidelines and messaging and the development of clinical practice guidelines. Upstream solutions including regulatory action on chemicals and heightened attention to environmental justice would result in optimal management of this issue.

Earliest Pottery on New Guinea Mainland Reveals Austronesian Influences in Highland Environments 3000 Years Ago.

Austronesian speaking peoples left Southeast Asia and entered the Western Pacific c.4000-3000 years ago, continuing on to colonise Remote Oceania for the first time, where they became the ancestral populations of Polynesians. Understanding the impact of these peoples on the mainland of New Guinea before they entered Remote Oceania has eluded archaeologists. New research from the archaeological site of Wañelek in the New Guinea Highlands has broken this silence. Petrographic and geochemical data from pottery and new radiocarbon dating demonstrates that Austronesian influences penetrated into the highland interior by 3000 years ago. One potsherd was manufactured along the northeast coast of New Guinea, whereas others were manufactured from inland materials. These findings represent the oldest securely dated pottery from an archaeological context on the island of New Guinea. Additionally, the pottery comes from the interior, suggesting the movements of people and technological practices, as well as objects at this time. The antiquity of the Wañelek pottery is coincident with the expansion of Lapita pottery in the Western Pacific. Such occupation also occurs at the same time that changes have been identified in subsistence strategies in the archaeological record at Kuk Swamp suggesting a possible link between the two.

Factors affecting compliance with clinical practice guidelines for pap smear screening among healthcare providers in africa: systematic review and meta-summary of 2045 individuals.

BACKGROUND: Although the importance of the Pap smear in reducing cancer incidence and mortality is known, many countries in Africa have not initiated yet widespread national cervical cancer screening programs. The World Health Organization (WHO) has published Clinical Practice Guidelines (CPGs) on cervical cancer screening in developing countries; however, there is a gap between expectations and clinical performance. Thus, the aim of this study was to conduct a systematic review and meta-summary to identify factors affecting compliance with CPGs for Pap screening among healthcare providers in Africa. METHODS: And Findings: MEDLINE, Scirus, Opengate and EMBASE databases were searched in January 2012. Studies involving medical personnel practicing in Africa, whose outcome measured any factors that affect medical personnel from using a Pap smear to screen for cervical cancer, were included. Two reviewers independently evaluated titles and abstracts, then full-texts, extracted data and assessed quality of the included studies. A descriptive analysis of the included studies was conducted. We calculated Frequency effect sizes (FES) for each finding and Intensity effect sizes (IES) for each article to represent their magnitudes in the analyses. Of 1011 studies retrieved, 11 studies were included (2045 individuals). Six different themes related to the factors affecting compliance with CPGs were identified: Insufficient Knowledge/Lack of awareness (FES = 82%), Negligence/Misbeliefs (FES = 82%), Psychological Reasons (FES = 73%), Time/Cost Constraint (FES = 36%), Insufficient infrastructure/training (FES = 45%) and also no reason given (FES = 36%). IES for articles ranged between 33 and 83%. CONCLUSIONS: These results suggest that prevention initiatives should be comprehensive to include education and resources needs assessments and improvement, Pap smear test training, strategies on costing, and practitioner time studies.

Chemical exposures of women workers in the plastics industry with particular reference to breast cancer and reproductive hazards.

Despite concern about the harmful effects of substances contained in various plastic consumer products, little attention has focused on the more heavily exposed women working in the plastics industry. Through a review of the toxicology, industrial hygiene, and epidemiology literatures in conjunction with qualitative research, this article explores occupational exposures in producing plastics and health risks to workers, particularly women, who make up a large part of the workforce. The review demonstrates that workers are exposed to chemicals that have been identified as mammary carcinogens and endocrine disrupting chemicals, and that the work environment is heavily contaminated with dust and fumes. Consequently, plastics workers have a body burden that far exceeds that found in the general public. The nature of these exposures in the plastics industry places women at disproportionate risk, underlining the importance of gender. Measures for eliminating these exposures and the need for regulatory action are discussed.

Protein microarray analysis of mammary epithelial cells from obese and nonobese women at high risk for breast cancer: feasibility data.

BACKGROUND: Obesity is a well-established risk factor for cancer, accounting for up to 20% of cancer deaths in women. Studies of women with breast cancer have shown obesity to be associated with an increased risk of dying from breast cancer and increased risk of developing distant metastasis. While previous studies have focused on differences in circulating hormone levels as a cause for increased breast cancer incidence in postmenopausal women, few studies have focused on potential differences in the protein expression patterns of mammary epithelial cells obtained from obese versus nonobese women. METHODS: Protein expression was assessed by reverse-phase protein microarray in mammary epithelial cells from 31 random periareolar fine needle aspirations performed on 26 high-risk women. RESULTS: In this pilot and exploratory study, vimentin (unadjusted P=0.028) expression was significantly different between obese and nonobese women. CONCLUSIONS: Vimentin is integral both to adipocyte structure and function and to the epithelial-to-mesenchymal transition needed for cancer cell metastasis. Further research is needed to confirm this finding and determine the possible effects of the adipocyte microenvironment on the initiation and progression of breast cancer in high-risk women. IMPACT: Differential protein expression patterns obtained from a future expanded study may serve to elaborate the underlying pathology of breast cancer initiation and progression in obese women and identify potential biomarkers of response to preventative interventions such as dietary changes and exercise.

Human adaptation and plant use in highland New Guinea 49,000 to 44,000 years ago.

After their emergence by 200,000 years before the present in Africa, modern humans colonized the globe, reaching Australia and New Guinea by 40,000 to 50,000 years ago. Understanding how humans lived and adapted to the range of environments in these areas has been difficult because well-preserved settlements are scarce. Data from the New Guinea Highlands (at an elevation of ~2000 meters) demonstrate the exploitation of the endemic nut Pandanus and yams in archaeological sites dated to 49,000 to 36,000 years ago, which are among the oldest human sites in this region. The sites also contain stone tools thought to be used to remove trees, which suggests that the early inhabitants cleared forest patches to promote the growth of useful plants.