Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

BACKGROUND: Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites. OBJECTIVES: To identify factors contributing to therapy failure. METHODS: Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained. RESULTS: Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary. CONCLUSIONS: The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

HIV Infection Progression Monitoring System Based on CD4 Counts and Wishart Distribution.

The human immunodeficiency virus (HIV) is a viral infection that destroys the human immune system, resulting in the acquired immunodeficiency syndrome (AIDS). The management and care of patients on antiretroviral therapy (ART) consumes a large portion of the health budget of many countries. ART improves the lives of the HIV patients. However, benefiting from the treatment remains to be low due to the nonadherence, adverse events, and treatment failure associated with the transmitted drug resistance mutations (TDRMs). Extra care is therefore required in prescribing switch of ART regimens for HIV-naive patients. We propose a disease monitoring system, which depends on how the HIV-naive patients respond to the ART regimen. We model cluster of differentiation 4 (CD4) counts data measured at every 3 months in a period of 48 weeks on a cohort of 87 HIV-naive patients on ART, from Zambia. We demonstrate how to apply the Bayesian Wishart distribution to model CD4 counts, leading to an informative HIV progression monitoring system. We found a steady increase in the average of the CD4 counts (from 219 to 315) for HIV-naive patients on the ART regimen. The average was still below the expected 500 CD4 counts for a normal person. The derived precision matrix shows an increase in probability of potency of the ART regimen, which ranges from 0.1261 to 0.8678. An early detection is crucial as it allows for timely switch of regimen from first to second line or to the third line. The proposed HIV disease progression monitoring system for HIV-naive patients on ART regimen that is based on CD4 counts could enable physicians make informed decisions on the management and care of the patients.

Correction: Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Correction for 'Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions' by J. A. Perlinger et al., Environ. Sci.: Processes Impacts, 2018, 20, 195-209.

Discovery and characterization of a positive allosteric modulator of transient receptor potential canonical 6 (TRPC6) channels.

The non-selective second messenger-gated cation channel TRPC6 (transient receptor potential canonical 6) is activated by diacylglycerols (DAG) in a PKC-independent manner and plays important roles in a variety of physiological processes and diseases. In order to facilitate novel therapies, the development of potent inhibitors as well as channel-activating agents is of great interest. The screening of a chemical library, comprising about 17,000 small molecule compounds, revealed an agent, which induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in a concentration-dependent manner (EC50 = 2.37 ± 0.25 µM) in stably TRPC6-expressing HEK293 cells. This new compound (C20) selectively acts on TRPC6, unlike OAG (1-oleoyl-1-acetyl-sn-glycerol), which also activates PKC and does not discriminate between TRPC6 and the closely related channels TRPC3 and TRPC7. Further evaluation by Ca2+ assays and electrophysiological studies revealed that C20 rather operated as an enhancer of channel activation than as an activator by itself and led to the assumption that the compound C20 is an allosteric modulator of TRPC6, enabling low basal concentrations of DAG to induce activation of the ion channel. Furthermore, C20 was tested in human platelets that express TRPC6. A combined activation of TRPC6 with C20 and OAG elicited a robust increase in [Ca2+]i in human platelets. This potentiated channel activation was sensitive to TRPC6 channel blockers. To achieve sufficient amounts of C20 for biological studies, we applied a one-pot synthesis strategy. With regard to studies in native systems, the sensitizing ability of C20 can be a valuable pharmacological tool to selectively exaggerate TRPC6-dependent signals.

Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Mercury (Hg) emissions pose a global problem that requires global cooperation for a solution. However, neither emissions nor regulations are uniform world-wide, and hence the impacts of regulations are also likely to vary regionally. We report here an approach to model the effectiveness of regulations at different scales (local, regional, global) in reducing Hg deposition and fish Hg concentrations in the Laurentian Great Lakes (GL) region. The potential effects of global change on deposition are also modeled. We focus on one of the most vulnerable communities within the region, an Indigenous tribe in Michigan's Upper Peninsula (UP) with a high fish consumption rate. For the GL region, elements of global change (climate, biomass burning, land use) are projected to have modest impacts (<5% change from the year 2000) on Hg deposition. For this region, our estimate of the effects of elimination of anthropogenic emissions is a 70% decrease in deposition, while our minimal regulation scenario increases emissions by 35%. Existing policies have the potential to reduce deposition by 20% with most of the reduction attributable to U.S. policies. Local policies within the Great Lakes region show little effect, and global policy as embedded in the Minamata Convention is projected to decrease deposition by approximately 2.8%. Even within the GL region, effects of policy are not uniform; areas close to emission sources (Illinois, Indiana, Ohio, Pennsylvania) experience larger decreases in deposition than other areas including Michigan's UP. The UP landscape is highly sensitive to Hg deposition, with nearly 80% of lakes estimated to be impaired. Sensitivity to mercury is caused primarily by the region's abundant wetlands. None of the modeled policy scenarios are projected to reduce fish Hg concentrations to the target that would be safe for the local tribe. Regions like Michigan's UP that are highly sensitive to mercury deposition and that will see little reduction in deposition due to regulations require more aggressive policies to reduce emissions to achieve recovery. We highlight scientific uncertainties that continue to limit our ability to accurately predict fish Hg changes over time.

Fitness, obesity and risk of asthma among Army trainees.

BACKGROUND: Epidemiological data suggest an association between overweight/obesity and asthma. However, less is known about the relationship between physical fitness and asthma. AIMS: To enumerate new-onset asthma diagnoses in Army recruits during the first 2 years of service and determine associations with fitness and excess body fat (EBF) at military entrance. METHODS: New asthma diagnoses over 2 years in Army recruits at six entrance stations were obtained from military health and personnel records. Poisson regression models were used to determine associations of asthma diagnosis with pre-accession fitness testing, EBF and other potential factors. RESULTS: In 9979 weight-qualified and 1117 EBF entrants with no prior history of asthma, 256 new cases of asthma were diagnosed within 2 years of military entry. Low level of fitness, defined by a step test and EBF, was significantly associated with new asthma diagnosis [adjusted incidence rate ratio (IRR), 1.47; 95% confidence interval (CI) 1.11-1.96 and adjusted IRR, 1.53; 95% CI 1.06-2.20, respectively]. CONCLUSIONS: Individuals with low fitness levels, EBF or both are at higher risk of asthma diagnosis in the first 2 years of military service.

Fitness, obesity and risk of heat illness among army trainees.

BACKGROUND: Exertional heat illness (EHI) affects military personnel, athletes and occupational groups such as agricultural workers, despite knowledge of preventive measures. AIMS: To evaluate EHI diagnoses during US Army basic training and its associations with fitness and body fat on entering military service. METHODS: From February 2005 to September 2006, US Army recruits at six different military entrance stations took a pre-accession fitness test, including a 5-min step test scored as pass or fail. Subsequent EHI incidence and incidence rate ratios were analysed with reference to subjects' fitness (step test performance) and whether they met (weight qualified [WQ]) or exceeded body fat (EBF) standards. RESULTS: Among the 8621 WQ and 834 EBF male subjects, there were 67 incidents of EHI within 180 days of entering military service. Among WQ subjects, step test failure was significantly associated with EHI (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.13, 3.53). For those passing the step test, the risk of EHI was significantly higher in EBF than in WQ subjects (OR 3.98, 95% CI 2.17, 7.29). Expected ORs for the joint effects of step test failure and EBF classification under additive and multiplicative models were 4.98 and 7.96, respectively. There were too few women to evaluate their data in detail. CONCLUSIONS: This study demonstrated that fitness and body fat are independently associated with incident EHI, and the effect of both was substantially higher. Those with low fitness levels and/or obesity should be evaluated further before engaging in intense physical activity, especially in warmer months.

Striatal dopamine release in schizophrenia comorbid with substance dependence.

Dopamine (DA) has a role in the pathophysiology of schizophrenia and addiction. Imaging studies have indicated that striatal DA release is increased in schizophrenia, predominantly in the precommissural caudate (preDCA), and blunted in addiction, mostly in the ventral striatum (VST). Therefore, we aimed to measure striatal DA release in patients with comorbid schizophrenia and substance dependence. We used [(11)C]raclopride positron emission tomography and an amphetamine challenge to measure baseline DA D2-receptor availability (BPND) and its percent change post-amphetamine (ΔBPND, to index amphetamine-induced DA release) in striatal subregions in 11 unmedicated, drug-free patients with both schizophrenia and substance dependence, and 15 healthy controls. There were no significant group differences in baseline BPND. Linear mixed modeling using ΔBPND as the dependent variable and striatal region of interest as a repeated measure indicated a significant main effect of diagnosis, F(1,24)=8.38, P=0.008, with significantly smaller ΔBPND in patients in all striatal subregions (all P ≤ 0.04) except VST. Among patients, change in positive symptoms after amphetamine was significantly associated with ΔBPND in the preDCA (rs=0.69, P=0.03) and VST (rs=0.64, P=0.05). In conclusion, patients with comorbid schizophrenia and substance dependence showed significant blunting of striatal DA release, in contrast to what has been found in schizophrenia without substance dependence. Despite this blunting, DA release was associated with the transient amphetamine-induced positive-symptom change, as observed in schizophrenia. This is the first description of a group of patients with schizophrenia who display low presynaptic DA release, yet show a psychotic reaction to increases in D2 stimulation, suggesting abnormal postsynaptic D2 function.

Health claims assessment in the field of joint and cartilage: a consensus viewpoint of the Group for the Respect of Ethics and Excellence in Science.

INTRODUCTION: In 2006, the European Parliament and Council issued a regulation (No. 1924/2006) for the nutrition and health claims made on foods, including food supplements. According to the regulation, the use of nutrition and health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. In the field of joint and cartilage health, there is no clear scientific-based definition of the nature of such a beneficial nutritional or physiological effect. The objective of this paper is to scientifically define the possible content of health claims related to joint and cartilage health and to provide scientific guidelines for the design of clinical studies which need to be adopted to substantiate such health claims. METHODS: Literature review up to September 2011 followed by a consensus expert discussion organized by the Group for the Respect of Ethics and Excellence in Science (GREES). RESULTS: In line with the general principles of the PASSCLAIM and the Codex recommendations, the GREES identified four acceptable health claims related to joint and cartilage health based on the effects on discomfort, joint and cartilage structural integrity or risk factors for joint and cartilage diseases. The GREES considers that randomized controlled trials on a relevant outcome is the best design to assess health claims. Moreover, animal studies could also be of interest to substantiate some health claims, to assess the clinical relevance of endpoints used in human studies or to extrapolate data obtained in patients to the target (apparently) healthy population. CONCLUSION: According to the methodology and biomarkers used in the study and whether or not additional animal studies are provided to support the claim, various health claims can be acceptable in the field of joint and cartilage health.

Designing early detection programs for ovarian cancer.

Human epididymis protein 4 (HE4) shows promise as a serum marker that complements CA125 in the early detection of epithelial ovarian cancer, either as a first-line screen or as a second-line screen in a multimodal strategy. Incorporation of symptoms in a screening strategy that includes CA125 and HE4 may warrant further research.

Musculoskeletal injuries among overweight army trainees: incidence and health care utilization.

BACKGROUND: Musculoskeletal injuries are a major cause of morbidity in military training. They are more common among overweight/obese individuals, and the prevalence of overweight/obesity in the military has increased. During strong economic periods, the military can be challenged to recruit enough qualified personnel, and physical standards are sometimes relaxed. AIMS: This study was conducted to compare the incidence of and outpatient utilization for training-related overuse injuries among men who were over body fat (OBF) standards compared with those who were weight qualified (WQ). METHODS: All study subjects were men ≥18 years old, who were classified as OBF or WQ and were followed for 90 days. During this period, everyone entering through the study sites was required to take a physical fitness test (5 min step test). Only individuals passing the fitness test were included in these analyses. RESULTS: There were 812 OBF and 6511 WQ study participants. OBF were 47% more likely to experience a musculoskeletal injury and had 49% higher health care utilization. Other significant factors included age >19 and a history of smoking. CONCLUSIONS: Among this population who had passed a fitness test, those who were OBF had a substantially higher risk of injury and higher utilization for these injuries. Because the recruiting environment is much better, military entrance standards have been tightened, but should the economy improve substantially the military may again be challenged to recruit adequate numbers of personnel, and the lessons learned in this project may prove valuable.

BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease.

Brain-derived neurotrophic factor (BDNF) is the main candidate for neuroprotective therapeutic strategies for Huntington's disease. However, the administration system and the control over the dosage are still important problems to be solved. Here we generated transgenic mice overexpressing BDNF under the promoter of the glial fibrillary acidic protein (GFAP) (pGFAP-BDNF mice). These mice are viable and have a normal phenotype. However, intrastriatal administration of quinolinate increased the number of reactive astrocytes and enhanced the release of BDNF in pGFAP-BDNF mice compared with wild-type mice. Coincidentally, pGFAP-BDNF mice are more resistant to quinolinate than wild-type mice, suggesting a protective effect of astrocyte-derived BDNF. To verify this, we next cultured astrocytes from pGFAP-BDNF and wild-type mice for grafting. Wild-type and pGFAP-BDNF-derived astrocytes behave similarly in nonlesioned mice. However, pGFAP-BDNF-derived astrocytes showed higher levels of BDNF and larger neuroprotective effects than the wild-type ones when quinolinate was injected 30 days after grafting. Interestingly, mice grafted with pGFAP-BDNF astrocytes showed important and sustained behavioral improvements over time after quinolinate administration as compared with mice grafted with wild-type astrocytes. These findings show that astrocytes engineered to release BDNF can constitute a therapeutic approach for Huntington's disease.

[Correlation of back pain and magnetic resonance imaging of the lumbar spine in elite horse vaulters]. / Zusammenhang zwischen Rückenschmerzen und kernspintomografischen LWS-Befunden bei Hochleistungsvoltigierern.

INTRODUCTION: A connection between morphologic lesions of the spine and specific sport disciplines incorporating torsional and hyperextension forces has been found. Although vaulting incorporates a significant amount of figures known from gymnastics, little is known about the influence of this sport on the lower back. The aim of our study was to assess to what extent vaulters suffer from back pain and whether these symptoms correlate to findings in magnetic resonance imaging (MRI) of the lumbar spine. METHODS: 20 high level vaulters ( [see text] age 21.95 [15 - 36] years) were included in the study. Using a standardised questionnaire biometric data, training intensity, localisation as well as intensity of back pain (VAS) was assessed. 12 of these vaulters agreed to an MRI scan of their lumbar spine. Scans were evaluated for morphologic changes using a semiquantative score and the results were correlated to clinical symptoms. RESULTS: 17 / 20 (85 %) reported of back pain of which 15 (75 %) had daily pain, the remaining 2 only occasionally. The average pain intensity on the visual analogue scale (VAS) was reported to be 3.76 +/- 0.53. The MRI scans revealed only slight degenerative changes of the lumbar spine. Statistical analysis of the data (Spearman's rank test) could not show a significant correlation between clinical symptoms and morphologic MRI-changes. CONCLUSION: Vaulters, compared to riders of other disciplines, seem to suffer from recurrent back pain to a greater extent. Despite the fact that the lumbar spine is confronted with repetitive torsional and hyperextension forces, vaulters do not show undue early degenerative changes or marked lesions of the lumbar spine. Recurrent back pain in the vaulter is most likely due to functional problems. It seems unlikely that is based on manifest morphologic changes of the lower back.

[Influence of the riding discipline and riding intensity on the incidence of back pain in competitive horseback riders]. / Einfluss der Reitdisziplin und -intensität auf die Inzidenz von Rückenschmerzen bei Reitsportlern.

INTRODUCTION: The connection between morphologic changes of the spine and the intensity of training has been assessed for a number of sport activities. The influence of horseback riding on the spine has only rarely been evaluated. The aim of our study was to evaluate to what degree horseback riders suffer from back pain and whether there is an association between this parameter and the category i. e. the intensity of horseback riding. Furthermore we wanted to judge whether riding may have a positive effect on pre-existent back pain. METHODS: 508 horseback riders (63.2 % females; 36.8 % males) competing in either dressage, showjumping or vaulting were interviewed using a questionnaire. Apart from biometric data, the intensity with which riding was performed and the localisation and intensity (VAS) of back pain was assessed. Furthermore, in the case of existing back pain, riders were asked whether different riding disciplines and paces changed the intensity of pain. RESULTS: 300 dressage riders (59.1 %), 188 showjumpers (37.0 %) and 20 vaulters (3.9 %) with an average age of 33.5 Jahre (12 - 77 years) were questioned. The incidence of back pain was 72.5 %. A significant correlation between back pain and riding discipline respectively gender or riding level could not be found. Discrepancies in VAS-score for dressage riders (3.95 +/- 0.13), show jumpers (4.10 +/- 0.16) and vaulters (3.76 +/- 0.5) were marginal and not significant (p > 0.05). Overall 58.7 % resp. 15.2 % reported to have pain in the lumbar i.e cervical spine. Despite the fact that a large fraction of dressage riders claimed to have problems in these spine areas with 57.7 % resp. 68.8 %, this finding was not significant compared to the other riding disciplines. While 61.6 % of dressage riders reported an improvement of their back pain when riding, this was only the case in 40.9 % of show jumpers. CONCLUSION: Compared to the general population, a high incidence of back pain is found among riders. A significant correlation between the intensity of riding or the riding discipline and frequency or severity of back pain could not be found. For riders with pre-existent back pain the pace "walk" seems to have a positive influence on pain intensity.

Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells.

The use of stem cells for reconstructive or neuroprotective strategies can benefit from new advances in neuroimaging techniques to track grafted cells. In the present work, we analyze the potential of a neural stem cell (NSC) line, which stably expresses the glial cell line-derived neurotrophic factor (GDNF) and the firefly luciferase gene (GDNF/Luc-NSC), for cell therapy in a Huntington's disease mouse model. Our results show that detection of light photons is an effective method to quantify the proliferation rate and to characterize the migration pathways of transplanted NSCs. Intravenous administration of luciferine, the luciferase substract, into the grafted animals allowed the detection of implanted cells in real time by an optical neuroimaging methodology, overpassing the limits of serial histological analyses. We observed that transplanted GDNF/Luc-NSCs survive after grafting and expand more when transplanted in quinolinate-lesioned nude mouse striata than when transplanted in non-lesioned mice. We also demonstrate that GDNF/Luc-NSCs prevent the degeneration of striatal neurons in the excitotoxic mouse model of Huntington's disease and reduce the amphetamine-induced rotational behavior in mice bearing unilateral lesions.

Sediment radioisotope dating across a stratigraphic discontinuity in a mining-impacted lake.

Application of radioisotope sediment dating models to lakes subjected to large anthropogenic sediment inputs can be problematic. As a result of copper mining activities, Torch Lake received large volumes of sediment, the characteristics of which were dramatically different from those of the native sediment. Commonly used dating models (CIC-CSR, CRS) were applied to Torch Lake, but assumptions of these methods are violated, rendering sediment geochronologies inaccurate. A modification was made to the CRS model, utilizing a distinct horizon separating mining from post-mining sediment to differentiate between two focusing regimes. (210)Pb inventories in post-mining sediment were adjusted to correspond to those in mining-era sediment, and a sediment geochronology was established and verified using independent markers in (137)Cs accumulation profiles and core X-rays.

Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma.

OBJECTIVES: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier. METHODS: We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program. RESULTS: CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125. CONCLUSION: The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.

Current research and treatment for epithelial ovarian cancer. A Position Paper from the Helene Harris Memorial Trust.

In March 2003, an international mulltidisciplinary group of scientists and clinicians with a specific interest in ovarian cancer met for 4 days to discuss research into and treatment of this challenging disease. Under the headings of molecular genetics, molecular biology, the biology of ovarian cancer, old therapies, new targets and the early detection of the disease, this Position Paper summarises the presentations and discussion from the 9th Biennial Helene Harris Memorial Trust Forum on Ovarian Cancer. In particular, we highlight the potential of international collaborations in translating laboratory science into useful clinical interventions.

Breast cancer worry and mammography use by women with and without a family history in a population-based sample.

Worry about breast cancer risk has been found to be a barrier to mammography use by women with a family history of breast cancer in some studies, although worry is generally found to increase mammography use among average risk women. Our study sought to examine the association of worry with mammography use in a population-based sample of women stratified by family history associated risk for breast cancer. A population-based sample of 6512 women completed a telephone interview. Fourteen percent (n = 948) of these reported a family history suggestive of elevated risk, including at least one affected first-degree relative. To examine the effects of worry on mammography use in women, a logistic regression model, including family history associated risk, age, and worry, was tested. Although family history was a significant predictor of mammography use in bivariate examinations, in the multivariate model it was not significant after adjustment for age and worry, which remained statistically significant predictors of mammography (P < 0.05). The association between worry and mammography use was best described by a quadratic term. Interaction terms for family history-associated risk and worry were not statistically significant predictors of mammography use. Worry about breast cancer risk appears to be associated with mammography use in an inverted u-shaped pattern. Women reporting moderate levels of worry were more likely to use mammography annually than those who were either mildly or severely worried. Severe worry may be a barrier to mammography use for all women not only those with a family history.

Worry about ovarian cancer risk and use of ovarian cancer screening by women at risk for ovarian cancer.

OBJECTIVE: This study examined reports of perceived risk of ovarian cancer, worry, and screening use in a large sample of women. While screening for asymptomatic women is not generally recommended, in 1994 a consensus conference concluded that women with multiple affected relatives are at high risk for ovarian cancer and should be encouraged to participate in screening. The consensus report also suggested that women with a single affected first-degree relative are at elevated risk and while these women were not encouraged to get screening it was suggested that they may choose to pursue screening outside of a randomized trial [NIH Consensus Conference. JAMA 1995;273(6) 491-7]. METHODS: A total of 3257 women participated in this research by completing a mailed survey on ovarian cancer risk, worry, and use of screening. One hundred forty-two of these women were at high risk for this disease due to a strong family history. An additional 144 women were at elevated risk due to a single first-degree affected relative with ovarian cancer. RESULTS: Family history did predict perceived risk, difficulties due to worry, and use of ovarian cancer screening. However, the group of women most likely to report high levels of perceived risk and to have received screening for ovarian cancer were women with a single affected relative rather than those at high risk, for whom screening is recommended. CONCLUSIONS: These results suggest that many women need additional education about ovarian cancer risk. Most women overestimated their risk for this disease. Some average-risk women get screening although it is not recommended outside of randomized trials, and a significant percentage of women at high risk fail to get recommended screening.